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Cheng R, Wang J, Wu Q, Peng P, Liao G, Luo X, Liang Z, Huang J, Qin M. The Predictive Value of Serum DAO, HDC, and MMP8 for the Gastrointestinal Injury in the Early Stage of Acute Pancreatitis in an Animal Model and a Clinical Study. Int J Gen Med 2024; 17:1937-1948. [PMID: 38736673 PMCID: PMC11088402 DOI: 10.2147/ijgm.s461352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 05/01/2024] [Indexed: 05/14/2024] Open
Abstract
Purpose This study was aimed at exploring the use of the acute gastrointestinal injury (AGI) grade and sensitive biomarkers to investigate gastrointestinal (GI) injury in early stage of acute pancreatitis (AP). Patients and Methods The AGI grade was used to evaluate intestinal function. Any GI injury above grade I (grades II-IV) was considered as severe. An AP rat model was created by retrograde injection of 4% sodium taurocholate. The pancreatic and intestinal histopathology scores were calculated by hematoxylin-eosin staining. Human and rat sera were assessed using ELISA. Tight junction (TJ) proteins were detected by Western blotting. Results In clinical study, the GI injury rate in mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) groups was 26.8%, 78.4%, and 94.8%, respectively (P < 0.05). Diamine oxidase (DAO), histidine decarboxylase (HDC), and matrix metalloproteinase 8 (MMP8) serum levels were higher in AP patients than in healthy people (P < 0.05). Patients with GI injury had higher serum levels of DAO, HDC, and MMP8 than those without GI injury (P < 0.05). In animal experiments, the serum levels of DAO, HDC, and MMP8 were higher in the AP group than in normal and sham-operated (SO) groups (P < 0.05). The expressions of tricellulin, claudin-1, ZO-1, and occludin were significantly lower in the AP group than in normal and SO groups (P < 0.05). Conclusion The serum levels of DAO, HDC, and MMP8 are novel biomarkers of GI injury in the early stage of AP; their elevation indicates the development of GI injury in AP. The intestinal TJ disruption may be a primary mechanism of GI injury and requires more in-depth research.
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Affiliation(s)
- Ruoxi Cheng
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Jie Wang
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Qing Wu
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Peng Peng
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Guolin Liao
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Xiuping Luo
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Zhihai Liang
- Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Jiean Huang
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
| | - Mengbin Qin
- Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China
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Ueyama Y, Tokuhara K, Miki H, Nakatake R, Sakaguchi T, Nishizawa M, Kaibori M, Okumura T. Active Hexose Correlated Compound Has Protective Effects in Ischemia–Reperfusion Injury of the Rat Small Intestine. J Surg Res 2019; 243:265-273. [DOI: 10.1016/j.jss.2019.05.047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 05/17/2019] [Accepted: 05/29/2019] [Indexed: 12/29/2022]
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Martínez Moreno JM, Reyes-Ortiz A, Lage Sánchez JM, Sánchez-Gallegos P, Garcia-Caballero M. Timeline of Intestinal Adaptation After Malabsortive Surgery: Effect of Luminal Nutrients, Biliopancreatic Secretion, and Glutamine Supplementation. Obes Surg 2017; 27:3133-3141. [PMID: 28578495 DOI: 10.1007/s11695-017-2754-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND The aim of this study was to study the process of intestinal adaptation in the three limbs of the small intestine after malabsorptive bariatric surgery: the biliopancreatic limb, the alimentary limb, and the common channel. These limbs are exposed to different stimuli, namely, gastrointestinal transit and nutrients in the alimentary limb, biliopancreatic secretions in the biliopancreatic limb, and a mix of both in the common channel. We also wished to investigate the effect of glutamine supplementation on the adaptation process. METHODS Three types of surgery were performed using a porcine model: biliopancreatic bypass (BPBP), massive (75%) short bowel resection as the positive control, and a sham operation (transection) as the negative control. We measured the height and width of intestinal villi, histidine decarboxylase (HDC) activity, and amount of HDC messenger RNA (mRNA) (standard diet or a diet supplemented with glutamine). RESULTS An increase in HDC activity and mRNA expression was observed in the BPBP group. This increase coincided with an increase in the height and width of the intestinal villi. The increase in villus height was observed immediately after surgery and peaked at 2 weeks. Levels remained higher than those observed in sham-operated pigs for a further 4 weeks. CONCLUSIONS The intestinal adaptation process in animals that underwent BPBP was less intense than in those that underwent massive short bowel resection and more intense than in those that underwent transection only. Supplementation with glutamine did not improve any of the parameters studied, although it did appear to accelerate the adaptive process.
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Affiliation(s)
- José Manuel Martínez Moreno
- Department of Surgical Specialities, Biochemistry and Immunology, Faculty of Medicine, University of Málaga, 29071, Málaga, Spain.
| | | | | | - Pilar Sánchez-Gallegos
- Department of Surgical Specialities, Biochemistry and Immunology, Faculty of Medicine, University of Málaga, 29071, Málaga, Spain
| | - Manuel Garcia-Caballero
- Department of Surgical Specialities, Biochemistry and Immunology, Faculty of Medicine, University of Málaga, 29071, Málaga, Spain
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The role of mast cells in ischemia and reperfusion injury. Inflamm Res 2014; 63:899-905. [PMID: 25108401 DOI: 10.1007/s00011-014-0763-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2013] [Revised: 06/04/2014] [Accepted: 07/24/2014] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Ischemia and reperfusion (IR) injury is a challenging clinical problem that is triggered by ischemia in an organ followed by subsequent restoration of the blood supply. The effects of mast cell (MC) in IR injury are not totally clear. MATERIALS AND METHODS We review the body of literature on the role of MCs in IR injury based on an unrestricted Pubmed search for the descriptors "mast cell", "ischemia" and "reperfusion injury", as well as discuss implications for treatment and future directions. RESULTS Shortly after IR, chemicals released by MC can trigger vasoactive substance formation, tissue leakage, upregulation of adhesive molecules followed by leukocyte recruitment and infiltration, and pronecrotic pathway activation, among other physiologic changes. In the long term, MCs may influence tissue remodeling and repair as well as blood restoration after IR. Consistent with these findings, methods and drugs that target MCs have been shown to attenuate IR injury. CONCLUSION It has been demonstrated that MCs play a role in IR injury, but the mechanisms are complex and need to be further studied.
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Huang H, Ma J, Zhu W, Sun J, Yan K, Song B, Xue Y, Xin J, Pan W, Zhu H, Chen C. The application of polymerized porcine hemoglobin (pPolyHb) in the rat small bowel preservation. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2014; 42:289-95. [PMID: 24564347 DOI: 10.3109/21691401.2013.845571] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Small bowel transplantation (SBTx) has become a standard clinical treatment for short bowel syndrome or irreversible intestinal function failure. Optimum preservation of the organ is essential for the success of transplantation. In this study, pPolyHb was used as an additive to hypertonic citrate adenine solution (HCA) to provide oxygen for rat small bowel transplant. Rat small bowels were preserved in HCA, HCA with pPolyHb, and University of Wisconsin solution (UW) for 12, 24, and 36 h, respectively. The results suggested that the preservation effect of HCA with pPolyHb was comparable with the UW solution, and more effective than the HCA solution.
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Affiliation(s)
- He Huang
- College of Life Science, Northwest University , Xi'an , P. R. China
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Ku HJ, Kim HY, Kim HH, Park HJ, Cheong JH. Bile acid increases expression of the histamine-producing enzyme, histidine decarboxylase, in gastric cells. World J Gastroenterol 2014; 20:175-182. [PMID: 24415870 PMCID: PMC3886006 DOI: 10.3748/wjg.v20.i1.175] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Revised: 09/16/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of bile acid on the expression of histidine decarboxylase (HDC), which is a major enzyme involved in histamine production, and gene expression of gastric transcription factors upon cooperative activation.
METHODS: HDC expression was examined by immunohistochemistry, reverse transcriptase polymerase chain reaction, and promoter assay in human gastric precancerous tissues, normal stomach tissue, and gastric cancer cell lines. The relationship between gastric precancerous state and HDC expression induced by bile acid was determined. The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated. MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor (FXR), small heterodimer partner (SHP), and caudal-type homeodomain transcription factor (CDX)1 expression plasmids. The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay.
RESULTS: Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases. Here, we show that bile acid increased the expression of HDC, which is a rate-limiting enzyme of the histamine production pathway. FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression. In addition, the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression. We confirmed similar expression patterns for HDC, CDX1, and SHP in patient tissues.
CONCLUSION: HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR, SHP, and CDX1.
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Ishihara H, Tanaka I, Yakumaru H, Tanaka M, Yokochi K, Akashi M. Pharmaceutical drugs supporting regeneration of small-intestinal mucosa severely damaged by ionizing radiation in mice. JOURNAL OF RADIATION RESEARCH 2013; 54:1057-64. [PMID: 23728323 PMCID: PMC3823793 DOI: 10.1093/jrr/rrt077] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Revised: 04/25/2013] [Accepted: 04/28/2013] [Indexed: 05/22/2023]
Abstract
Accidental exposure of the abdomen to high-dose radiation leads to severe consequences initiated by disruption of the mucosa in the small intestine. Therapeutic options are limited, even though various treatments have been investigated, particularly in the field of regenerative therapy. In order to identify readily available treatment methods, we included several current pharmaceutical drugs, for which the clinical trials have already been completed, in tests on mice that had undergone severe mucosal damage by radiation. The drugs were injected into mice 24 h after exposure to 15.7 Gy X-rays. The effects of the drugs on the damaged mucosa of the small intestine were evaluated using early regeneration indices [the expression of c-myb mRNA, and proliferation of epithelial cells in the form of microcolonies (MCs) by Days 4 and 5 post-irradiation] and the survival rate of the mice. Enhancement of mucosal regeneration at Day 4 (c-myb: P < 0.01, MC: P < 0.05) and improvement of the survival rate (P < 0.05) were observed when a clinical dose of gonadotropin, a stimulator of androgen, was injected. Similarly, a clinical dose of thiamazole (which prevents secretion of thyroid hormone) stimulated mucosal growth by Day 5 (c-myb: P < 0.01, MC: P < 0.05) and also improved the survival rate (P < 0.05). The nonclinical drugs histamine and high-dose octreotide (a growth hormone antagonist) also gave significant survival-enhancing benefits (P < 0.01 and P < 0.05, respectively). These results can be used to construct therapeutic programs and applied in various experimental studies to control the regeneration of damaged mucosa.
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Affiliation(s)
- Hiroshi Ishihara
- Corresponding author. Internal Decorporation Research Team, Research Program for Radiation Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba-shi, Chiba 263-8555, Japan. Tel: +81-43-206-3162; Fax: +81-43-284-1769;
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Chen G, Qiu Y, Sun L, Yu M, Wang W, Xiao W, Yang Y, Liu Y, Yang S, Teitelbaum DH, Ma Y, Lu D, Yang H. The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury. PLoS One 2013; 8:e76274. [PMID: 24098462 PMCID: PMC3789708 DOI: 10.1371/journal.pone.0076274] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Accepted: 08/26/2013] [Indexed: 12/27/2022] Open
Abstract
Background Notch signaling plays a critical role in the maintenance of intestinal crypt epithelial cell proliferation. The aim of this study was to investigate the role of Notch signaling in the proliferation and regeneration of intestinal epithelium after intestinal ischemia reperfusion (I/R) injury. Methods Male Sprague-Dawley rats were subjected to sham operation or I/R by occlusion of the superior mesenteric artery (SMA) for 20 min. Intestinal tissue samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of the intestinal epithelium was evaluated by immunohistochemical staining of proliferating nuclear antigen (PCNA). The mRNA and protein expression levels of Notch signaling components were examined using Real-time PCR and Western blot analyses. Immunofluorescence was also performed to detect the expression and location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the γ-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied to investigate the functional role of Notch signaling in the proliferation of intestinal epithelial cells in an in vitro IEC-6 culture system. Results I/R injury caused increased intestinal crypt epithelial cell proliferation and increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The immunofluorescence results further confirmed increased protein expression of Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression using siRNA both significantly inhibited the proliferation of IEC-6 cells. Conclusion The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in intestinal epithelium regeneration early after I/R injury by increasing crypt epithelial cell proliferation.
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Affiliation(s)
- Guoqing Chen
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yuan Qiu
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Lihua Sun
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Min Yu
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Wensheng Wang
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Weidong Xiao
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yang Yang
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yong Liu
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Songwei Yang
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Daniel H. Teitelbaum
- Department of Surgery, the University of Michigan Medical School, Ann Arbor, Michigan
| | - Yuanhang Ma
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Dingsong Lu
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Hua Yang
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
- * E-mail:
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Ji Y, Sakata Y, Li X, Zhang C, Yang Q, Xu M, Wollin A, Langhans W, Tso P. Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release. Am J Physiol Gastrointest Liver Physiol 2013; 304:G732-40. [PMID: 23413254 PMCID: PMC3625874 DOI: 10.1152/ajpgi.00399.2012] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Diamine oxidase (DAO) is abundantly expressed in mammalian small intestine catalyzing the oxidative breakdown of polyamines and histamine. The aim of this study was to determine the relationship between stimulation of intestinal diamine oxidase secretion with intestinal fat absorption and histamine release. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated and intraduodenal tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic DAO activity and protein secretion were analyzed by radiometric assay and Western blot, respectively. Lymphatic histamine concentration was measured by ELISA. Infusion of Liposyn II (4.43 kcal/3 ml) resulted in a ~3.5-fold increase in lymphatic DAO protein secretion and DAO activity, peaking at 1 h and lasting for 3 h. Liposyn II infusion also increased the lymphatic histamine release, a substrate for DAO. To determine the relationship of DAO release with histamine release, histamine was administered intraperitoneally (10 mg/kg) in fasting rats and resulted in a significant doubling in lymphatic DAO activity, supporting a link between histamine and DAO. In addition, ip administration of the histamine H4 receptor antagonist JNJ7777120 significantly reduced the Liposyn II-induced DAO output by 65.9%, whereas H(1) (pyrilamine maleate), H(2) (ranitidine), and H(3) (thioperamide maleate) receptor antagonists had little effect. We conclude that DAO secretion may contribute to the catabolism of histamine released during fat absorption and this is probably mediated through the histamine H(4) receptor.
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Affiliation(s)
- Yong Ji
- 1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
| | - Yasuhisa Sakata
- 1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
| | - Xiaoming Li
- 1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
| | - Chao Zhang
- 1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
| | - Qing Yang
- 1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
| | - Min Xu
- 1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
| | - Armin Wollin
- 2Department of Physiology, University of Saskatchewan, Saskatoon, Canada; and
| | - Wolfgang Langhans
- 3Physiology and Behavior Laboratory, Swiss Federal Institute of Technology, Schwerzenbach, Switzerland
| | - Patrick Tso
- 1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio;
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Carabajal E, Massari N, Croci M, Martinel Lamas DJ, Prestifilippo JP, Bergoc RM, Rivera ES, Medina VA. Radioprotective potential of histamine on rat small intestine and uterus. Eur J Histochem 2012; 56:e48. [PMID: 23361244 PMCID: PMC3567767 DOI: 10.4081/ejh.2012.e48] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Revised: 09/08/2012] [Accepted: 09/08/2012] [Indexed: 01/03/2023] Open
Abstract
The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239 ± 12 vs 160 ± 10; P<0.01). This effect was associated with a reduction of radiation-induced intestinal crypts apoptosis. Additionally, histamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats. The obtained evidences indicate that histamine is a potential candidate as a safe radioprotective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials.
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Affiliation(s)
- E Carabajal
- Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina
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von Rahden BHA, Jurowich C, Kircher S, Lazariotou M, Jung M, Germer CT, Grimm M. Allergic predisposition, histamine and histamine receptor expression (H1R, H2R) are associated with complicated courses of sigmoid diverticulitis. J Gastrointest Surg 2012; 16:173-82; discussion 182. [PMID: 21956435 DOI: 10.1007/s11605-011-1702-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2011] [Accepted: 09/14/2011] [Indexed: 01/31/2023]
Abstract
BACKGROUND We aimed to evaluate our hypothesis that allergic predisposition and expression of histamine receptors might contribute to complicated courses of sigmoid diverticulitis. METHODS Expression of histamine and histamine receptors (H1R, H2R) was analysed on protein level (immunohistochemistry/immunofluorescence (IF)) as well as mRNA level (reverse transcription-PCR (RT-PCR) in surgical specimen of patients (n = 101) having undergone resection for sigmoid diverticulits (n = 57 complicated diverticulitis/n = 44 non-complicated diverticulitis). RESULTS The mean number of comorbid diseases per patient was 1.76 ± 1.25. Thirty-nine of 101 patients (38.6%) exhibited allergic predisposition (grass poll, food, drug, pets, etc.). Comorbid diseases were significantly associated with complicated diverticulitis (p = 0.027). Complicated sigmoid diverticulitis was significantly associated with high H1R and H2R expression (p < 0.001). Furthermore, an association of complicated diverticulitis with allergic predisposition was found (odds ratio = 3.2, p = 0.0097). IF double-labelling experiments showed a strong correlation of increased histamine expression with expression of H1R and H2R on intestinal enterocytes (histamine/H1R, rho = 0.841, p < 0.0001 and histamine/H2R, rho = 0.806, p < 0.0001). The results of increased H1R and H2R expression in complicated sigmoid diverticulitis were also detected on mRNA level in a subset of patients (RT-PCR, p = 0.009). CONCLUSIONS Our findings suggest that allergic predisposition might be another important risk factor for complicated courses of acute sigmoid diverticulitis and linked with histamine receptor expression. Supportive therapies with antihistaminic drugs might become an option. Allergic predisposition might be worth considering when indicating surgery for sigmoid diverticulitis.
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Affiliation(s)
- Burkhard H A von Rahden
- Department of General-, Visceral-, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany.
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Yang JJ, Ma YL, Zhang P, Chen HQ, Liu ZH, Qin HL. Histidine decarboxylase is identified as a potential biomarker of intestinal mucosal injury in patients with acute intestinal obstruction. Mol Med 2011; 17:1323-37. [PMID: 21915437 PMCID: PMC3321802 DOI: 10.2119/molmed.2011.00107] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2011] [Accepted: 09/07/2011] [Indexed: 01/01/2023] Open
Abstract
Various biomarkers currently used for the diagnosis of intestinal mucosal injury (IMI) in patients with acute intestinal obstruction have low sensitivity and specificity. In the present study, IMI, as indicated by the impaired expression of tight junction proteins, including zonula occludens-1, occludin and claudin-1, and inflammation were determined in colonic tissues of patients with 45 strangulated intestinal obstruction (STR-IO) and the adjacent "normal" colonic tissues of 35 patients with colon cancers by quantitative real-time polymerase chain reaction (QRT-PCR), Western blotting, immunohistochemistry and histological examination, respectively. Then, two-dimensional fluorescent difference gel electrophoresis coupled with linear trap quadrupole mass spectrometry was used to screen for potential biomarkers of IMI in the serum samples of 10 STR-IO, 10 simple intestinal obstruction (SIM-IO) and 10 normal healthy controls. A total of 35 protein spots were differentially expressed among the serum samples, and six of the proteins were identified as potential biomarkers. Among the six proteins, histidine decarboxylase (HDC) and ceruloplasmin (CP) were elevated significantly in patients with STR-IO, compared with patients with SIM-IO and healthy controls. Thus, HDC and CP were further validated by QRT-PCR, Western blotting, immunohistochemistry and enzyme-linked immunosorbent assay, respectively, in colonic tissues, serum and urine samples. Finally, the receiver operating characteristic curves were used to show the area under the curves of HDC, CP and several established biomarkers, followed by the determination of the appropriate cutoff values and their sensitivities and specificities. It was shown that for serum and urine, HDC levels achieved sensitivities and specificities compatible to or even greater than those of established biomarkers for the diagnosis of IMI in patients with acute intestinal obstruction, although further validation in a larger cohort is required.
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Affiliation(s)
| | | | | | | | | | - Huan-Long Qin
- Address correspondence and reprint requests to Huan-Long Qin, Department of Surgery, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, P.R. China. Phone: +86 21 64361349; Fax: +86 21 64368920; E-mail:
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Medina VA, Croci M, Mohamad NA, Massari N, Garbarino G, Cricco GP, Núñez MA, Martín GA, Crescenti EJV, Bergoc RM, Rivera ES. Mechanisms underlying the radioprotective effect of histamine on small intestine. Int J Radiat Biol 2009; 83:653-63. [PMID: 17729160 DOI: 10.1080/09553000701570238] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
PURPOSE To examine the protective effects of histamine on intestinal damage produced by gamma-radiation. MATERIALS AND METHODS 56 mice were divided into 4 groups. Histamine and Histamine-10 Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued until the end of the experimental period; the untreated group received saline. Histamine-10 Gy and untreated-10 Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Small intestine was removed, fixed and stained with hematoxylin and eosin. The number of intestinal crypts per circumference, and other histological characteristics of intestinal cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA), Bax, Bcl-2 (pro- and anti-apoptotic protein, respectively), antioxidant enzymes (Superoxide dismutase (SOD), Catalase and Glutathione peroxidase), histamine content and apoptosis by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) assay. Cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. RESULTS Histamine treatment reduced mucosal atrophy, edema and preserved villi, crypts and nuclear and cytoplasmic characteristics of small intestine after radiation exposure. Additionally, histamine treatment increased PCNA expression and the BrdU-positive cell number, histamine content, decreased the number of apoptotic cells and significantly increased Catalase and copper-zinc-containing SOD of irradiated mice. CONCLUSIONS Histamine prevents radiation-induced toxicity by increasing proliferation of damaged intestinal mucosa and suppressing apoptosis that was associated with an increase in SOD and Catalase levels. This effect might be of clinical value in patients undergoing radiotherapy.
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Affiliation(s)
- Vanina A Medina
- Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires
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14
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Indigestible Material Attenuated Changes in Apoptosis in the Fasted Rat Jejunal Mucosa. Exp Biol Med (Maywood) 2008; 233:310-6. [DOI: 10.3181/0708-rm-228] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
We have previously demonstrated that fasting induced apoptosis and decreased cell proliferation in the rat intestinal mucosa. The aim was to investigate the effect of expanded polystyrene as indigestible material on apoptosis and cell proliferation in rat small intestinal mucosa during fasting. Male SD rats were divided into 3 groups. The first group was fed with chow and water ad libitum. The second group fasted for 72 hrs. The third group was fasted for 24 hrs and was fed expanded polystyrene. Intestinal apoptosis was evaluated by percent fragmented DNA assay, terminal deoxynucleotidyl transferase–mediated dUDP-biotin nick end-labeling (TUNEL) staining, and caspase-3 assay. Cell proliferation was analyzed by 5-bromo-2′-deoxyuridine (5-BrdU) uptake. Truncal vagotomy was performed to evaluate a role of the central nervous system. In the 72-hr fasted rat, mucosal height of the rat jejunum was decreased to 73% of that in rats fed ad libitum, and this decrease was partly restored to 90% in rats fed expanded polystyrene. The fragmented DNA was increased in fasted rats (28.0%) when compared with that in rats fed ad libitum (2.6%). The increase in fragmented DNA in fasted rats was recovered by feeding them expanded polystyrene (8.3%). TUNEL staining confirmed this result. The effect of polystyrene on apoptosis was decreased by truncal vagotomy. Expression of cleaved caspase-3 was increased in fasted rats, which was then decreased by feeding of expanded polystyrene. In contrast to apoptosis, feeding of expanded polystyrene had no reconstructive effect on 5-BrdU uptake in the intestinal epithelium, which was decreased by fasting to 60% of that in rats fed ad libitum. In conclusion, feeding of indigestible material partly restored the decrease in intestinal mucosal length in the fasted rats through the apoptotic pathway without any influence on BrdU uptake. Further exploration focused on the mechanism of this effect of indigestible material is required.
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15
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Lin T, Sakata H, Ootani A, Fujise T, Tsunada S, Amemori S, Danjo A, Yokoyama F, Sakata Y, Iwakiri R, Toda S, Fujimoto K. Apoptosis in rat jejunal mucosa is regulated partly through the central nervous system, which controls feeding behavior. J Gastroenterol Hepatol 2005; 20:1285-91. [PMID: 16048579 DOI: 10.1111/j.1440-1746.2005.03921.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
AIM The aim of this study was to investigate whether central nervous system-related feeding behavior regulates mucosal apoptosis in rat small intestines. METHODS The test solutions used in this study were an H(1) receptor antagonist (chlorpheniramine maleate), 2-deoxy-D-glucose, leptin, and 1-deoxy-D-glucosamine (2-amino-1,5-anhydro-2-deoxy-D-glucitol). Test solutions were injected into the third cerebroventricles of rats. Feeding behavior and jejunal apoptosis were evaluated both with and without truncal vagotomy. Intestinal apoptosis was evaluated by percentage fragmented DNA, electrophoresis, and TUNEL staining. RESULTS Chlorpheniramine and 2-deoxy-D-glucose elicited feeding, whereas leptin and 1-deoxy-D-glucosamine suppressed feeding. The test solutions, which elicited feeding (0.24 and 24 micromol/rat of chlorpheniramine and 2-deoxy-D-glucose, respectively), suppressed mucosal apoptosis in the rat jejunum 1 h after cerebroventricular infusion. In contrast, the test solutions, which suppressed feeding (8 and 24 micromol/rat of leptin and 1-deoxy-D-glucosamine, respectively), induced jejunal mucosal apoptosis 3 h after infusion. The effects of the test solutions on feeding behavior and changes in apoptosis were not affected by truncal vagotomy. CONCLUSION The central nervous system, which regulates feeding behavior, might control intestinal function through the regulation of intestinal apoptosis.
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Affiliation(s)
- Taisan Lin
- Department of Internal Medicine, Saga Medical School, Nabeshima, Saga 849-8501, Japan
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16
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Abstract
Oxido-reductive stress is a crucial factor of the tissue response during ischemia-reoxygenation injuries. Reperfusion affects primarily the microvasculature in a manner consistent with an acute inflammatory reaction. In this respect, the salient data suggest an important connection between endothelial cell-derived humoral mediators and the perivascular mast cell system. Increased endothelin-1 and decreased nitric oxide formation, mast cell degranulation and leukocyte accumulation coexist in gastrointestinal ischemia-reperfusion syndromes too. Constitutively produced nitric oxide inhibits, while increasingly formed endothelin-1 significantly enhances the degranulation of the intestinal mast cells. The endothelin-A receptor-dependent mast cell degranulation per se plays a secondary role in reperfusion-induced structural injury, but contributes significantly to leukocyte recruitment into the reperfused intestinal mucosa. It is conceivable therefore, that the nitric oxide--endothelin-1--mast cell cycle is involved in the mechanism of ischemia-reperfusion-induced endothelial cell-leukocyte interactions, where mast cells act to amplify the process of leukocyte sequestration. The alteration in the balance between endothelial cell-derived proadhesive vasoconstrictor and antiadhesive vasodilator factors exerts a significant influence on the mucosal integrity, and the antagonism of endothelin-A receptor activation in this setting tips the equilibrium toward tissue salvage.
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Affiliation(s)
- M Boros
- Institute of Surgical Research, University of Szeged, Szeged, Hungary.
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17
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Kojima M, Iwakiri R, Wu B, Fujise T, Watanabe K, Lin T, Amemori S, Sakata H, Shimoda R, Oguzu T, Ootani A, Tsunada S, Fujimoto K. Effects of antioxidative agents on apoptosis induced by ischaemia-reperfusion in rat intestinal mucosa. Aliment Pharmacol Ther 2003; 18 Suppl 1:139-45. [PMID: 12925152 DOI: 10.1046/j.1365-2036.18.s1.16.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM We have previously demonstrated that ischaemia-reperfusion induces apoptosis in the intestinal mucosa. To evaluate that reactive oxygen species enhanced intestinal apoptosis after ischaemia-reperfusion, we examined whether antioxidants reduced apoptosis. METHODS Rats were infused through a duodenal tube with antioxidative agents, glutathione, rebamipide and dymethylsulfoxide during 2 h before an ischaemic insult. The superior mesenteric artery was occluded for 60 min, followed by 60 min reperfusion. Apoptosis was evaluated by percentage fragmented DNA (fragmented DNA/total DNA) and immunochemical staining. RESULTS Increase in apoptosis in the intestinal mucosa after ischaemia-reperfusion was attenuated by intraduodenal infusion of antioxidative agents, but was not completely abolished. CONCLUSION Scavenging effects of the antioxidative agents attenuated increases in intestinal apoptosis, indicating that oxidative stress after ischaemia-reperfusion plays an important role in induction of apoptosis in the intestinal mucosa.
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Affiliation(s)
- M Kojima
- Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, Saga, Japan
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18
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Tunçel N, Tunçel M, Aboul-Enein HY. Effects of the vasoactive intestinal peptide on stress-induced mucosal ulcers and modulation of methylation of histamine in gastric tissue of the rats. FARMACO (SOCIETA CHIMICA ITALIANA : 1989) 2003; 58:449-54. [PMID: 12767385 DOI: 10.1016/s0014-827x(03)00060-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Vasoactive intestinal peptide (VIP) prevents stress-induced gastric ulcers, inhibits mast cell degranulation and protects gastric tissue from lipid peroxidation. Histamine has an important role in the development of gastric ulcers and mast cell derived histamine might be essential in this process.
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Affiliation(s)
- Nese Tunçel
- Department of Physiology, Faculty of Medicine, University of Osmangazi, 26040 Eskisehir, Turkey
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19
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Fujimoto K, Iwakiri R, Wu B, Fujise T, Tsunada S, Ootani A. Homeostasis in the small intestinal mucosa balanced between cell proliferation and apoptosis is regulated partly by the central nervous system. J Gastroenterol 2002; 37 Suppl 14:139-44. [PMID: 12572882 DOI: 10.1007/bf03326433] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The aim of this study was to investigate whether the central nervous system regulates mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase is a key enzyme for polyamine synthesis, which plays an important role in intestinal mucosal growth. The increase in ornithine decarboxylase activity in the duodenum just before a dark period was abolished by truncal vagotomy. An infusion of 2-deoxy-D-glucose into the third cerebroventricle activated the enzyme activity in the small intestine. Epithelial homeostasis is balanced by the regulation of cell proliferation and cell death. Intestinal mucosal apoptosis decreased in rats with ventromedial hypothalamus lesions, which induced hyperphagia and obesity. In contrast, sustained anorexia induced by 1-deoxy-D-glucosamine increased intestinal apoptosis. These results indicate that the central nervous system, in addition to local factors, is related to the regulation of mucosal homeostasis in the intestinal mucosa.
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Affiliation(s)
- Kazuma Fujimoto
- Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
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20
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Wu B, Iwakiri R, Tsunada S, Utsumi H, Kojima M, Fujise T, Ootani A, Fujimoto K. iNOS enhances rat intestinal apoptosis after ischemia-reperfusion. Free Radic Biol Med 2002; 33:649-58. [PMID: 12208351 DOI: 10.1016/s0891-5849(02)00917-6] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The aim of this study was to demonstrate (i) the role of iNOS (inducible nitric oxide synthase) on apoptosis in the rat intestinal mucosa after ischemia-reperfusion, and (ii) the effect of iNOS on the release of cytochrome c from mitochondria. The superior mesenteric artery was occluded for 60 min and was followed by a 60 min reperfusion. Rats were pretreated with an intraperitoneal injection of the following iNOS inhibitors: N-nitro-L-arginine methyl ester, aminoguanidine, and (1S,5S,6R,7R)-7- chloro-3-imino-5-methyl-2-azabicyclo [4. 1. 0] heptane hydrochloride (ONO-1714). Apoptosis was evaluated and NO(X) in the portal vein was assayed. The amount of iNOS, caspase-3, and cytochrome c were determined by a Western blot analysis. Intestinal mucosal epithelial mitochondrial dehydrogenase activity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoilium bromide. Ischemia-reperfusion increased intestinal mucosal apoptosis, NO(X) production in the portal vein, the amount of iNOS protein, and the release of cytochrome c, but not caspase-3. Inhibitors of iNOS significantly attenuated the induction of apoptosis, increased NO(X) production, and release of cytochrome c. Mitochondrial dysfunction was induced by ischemia-reperfusion, which was ameliorated by iNOS inhibitors. Our results indicate that iNOS is related to increased mucosal apoptosis in the rat small intestine after ischemia-reperfusion, which is partly explained by the release of cytochrome c from mitochondria to cytosols following mitochondrial dysfunction.
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Affiliation(s)
- Bin Wu
- Department of Internal Medicine, Saga Medical School, Nabeshima, Saga, Japan
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21
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Colucci R, Fleming JV, Xavier R, Wang TC. L-histidine decarboxylase decreases its own transcription through downregulation of ERK activity. Am J Physiol Gastrointest Liver Physiol 2001; 281:G1081-91. [PMID: 11557529 DOI: 10.1152/ajpgi.2001.281.4.g1081] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A poorly defined negative feedback loop decreases transcription of the L-histidine decarboxylase (HDC) gene. To help understand this regulation, we have studied the effect of HDC protein expression on HDC gene transcription in transfected AGS-B cells. Expression of the rat HDC protein inhibited HDC promoter activity in a dose-dependent fashion. The region of the HDC promoter mediating this inhibitory effect corresponded to a previously defined gastrin and extracellular signal-related kinase (ERK)-1 response element. Overexpression of the HDC protein reduced nuclear factor binding in this region. Experiments employing specific histamine receptor agonists indicated that the inhibitory effect was not dependent on histamine production, and studies with the HDC inhibitor alpha-fluoromethylhistidine revealed that inhibition was unrelated to enzyme activity. Instead, an enzymatically inactive region at the amino terminal of the HDC enzyme (residues 1-271) was shown to mediate inhibition. Fluorescent chimeras containing this domain were not targeted to the nucleus, arguing against specific inhibition of the HDC transcription machinery. Instead, we found that overexpression of HDC protein decreased ERK protein levels and ERK activity and that the inhibitory effect of HDC protein could be overcome by overexpression of ERK1. These data suggest a novel feedback-inhibitory role for amino terminal sequences of the HDC protein.
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Affiliation(s)
- R Colucci
- Harvard Medical School and Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
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22
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Yoshida T, Iwakiri R, Noda T, Okamoto K, Kojima M, Fukuyama K, Fujimoto K. Histaminergic effect on apoptosis of rat small intestinal mucosa after ischemia-reperfusion. Dig Dis Sci 2000; 45:1138-44. [PMID: 10877229 DOI: 10.1023/a:1005545801714] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This study aimed to examine the relationship between a harmful effect of histamine and apoptosis following ischemia-reperfusion in the rat intestine. The superior mesenteric artery was occluded for 60 min followed by reperfusion for 60 min. Rats were infused with H1-receptor antagonist (chlorpheniramine maleate) or H2-receptor antagonist (cimetidine). Additional rats were pretreated with aminoguanidine (100 mg/kg). Percent apoptosis in the intestinal mucosa increased after reperfusion, but neither H1 nor H2 antagonists had any effect on apoptosis. Aminoguanidine pretreatment inhibited activity of diamine oxidase and increased the plasma histamine concentration. Aminoguanidine attenuated the increase in mucosal apoptosis following reperfusion. Apoptosis induced by an ischemic insult to the intestinal mucosa was not related to an undesirable effect of histamine. Attenuation of increased intestinal apoptosis might be due to increased plasma histamine level and/or other pharmacological action of aminoguanidine, including inhibition of inducible nitric oxide synthase.
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Affiliation(s)
- T Yoshida
- Department of Internal Medicine, Saga Medical School, Nabeshima, Japan
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23
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Wessler S, Höcker M, Fischer W, Wang TC, Rosewicz S, Haas R, Wiedenmann B, Meyer TF, Naumann M. Helicobacter pylori activates the histidine decarboxylase promoter through a mitogen-activated protein kinase pathway independent of pathogenicity island-encoded virulence factors. J Biol Chem 2000; 275:3629-36. [PMID: 10652359 DOI: 10.1074/jbc.275.5.3629] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Helicobacter pylori infection of the gastric mucosa is accompanied by an activated histamine metabolism. Histamine plays a central role in the regulation of gastric acid secretion and is involved in the pathogenesis of gastroduodenal ulcerations. Histidine decarboxylase (HDC) is the rate-limiting enzyme for histamine production, and its activity is regulated through transcriptional mechanisms. The present study investigated the effect of H. pylori infection on the transcriptional activity of the human HDC (hHDC) promoter in a gastric epithelial cell line (AGS) and analyzed the underlying molecular mechanisms. Our studies demonstrate that H. pylori infection potently transactivated the hHDC promoter. The H. pylori-responsive element of the hHDC gene was mapped to the sequence +1 to +27 base pairs, which shows no homology to known cis-acting elements and also functions as a gastrin-responsive element. H. pylori regulates the activity of this element via a Raf-1/MEK/ERK pathway, which was activated in a Ras-independent manner. Furthermore, we found that H. pylori-induced transactivation of the hHDC promoter was independent of the cag pathogenicity island and the vacuolating cytotoxin A gene and therefore may be exerted through (a) new virulence factor(s). A better understanding of H. pylori-directed hHDC transcription can provide novel insights into the molecular mechanisms of H. pylori-dependent gene regulation in gastric epithelial cells and may lead to new therapeutic approaches.
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Affiliation(s)
- S Wessler
- Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Berlin, Germany
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24
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Tunçel N, Töre F, Sahintürk V, Ak D, Tunçel M. Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock. Peptides 2000; 21:81-9. [PMID: 10704723 DOI: 10.1016/s0196-9781(99)00177-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit. The present study showed that endotoxic shock did not lead to oxidative stress in either liver or kidney of the rats. On the other hand, mast cells, based on their location, displayed functional heterogeneity to the septic insults. VIP possibly modulated the specific reactions of the tissues to mediators released from mast cells during septic shock. The most prominent effect of VIP as compared to nitric oxide synthesis inhibition was related to mast cells. In conclusion, the prevention of mast cell reactivity by VIP could be a potential therapeutic strategy in controlling septic shock.
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Affiliation(s)
- N Tunçel
- Department of Physiology, Faculty of Medicine, University of Osmangazi, Meselik, Turkey.
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25
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Höcker M, Rosenberg I, Xavier R, Henihan RJ, Wiedenmann B, Rosewicz S, Podolsky DK, Wang TC. Oxidative stress activates the human histidine decarboxylase promoter in AGS gastric cancer cells. J Biol Chem 1998; 273:23046-54. [PMID: 9722530 DOI: 10.1074/jbc.273.36.23046] [Citation(s) in RCA: 51] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Oxidant stress is thought to play a role in the pathogenesis of many gastric disorders. We have recently reported that histidine decarboxylase (HDC) promoter activity is stimulated by gastrin through a protein kinase C- and extracellular signal-regulating kinase (ERK)-dependent pathway in gastric cancer (AGS-B) cells, and this transcriptional response is mediated by a downstream cis-acting element, the gastrin response element (GAS-RE). To study the mechanism through which oxidant stress affects gastric cells, we examined the effects of hydrogen peroxide (H2O2) on HDC promoter activity and intracellular signaling in AGS-B cells. H2O2 (10 mM) specifically activated the HDC promoter 10-12-fold, and this activation was blocked by both mannitol and N-acetylcysteine. Hydrogen peroxide treatment of AGS-B cells increased the phosphorylation and kinase activity of ERK-1 and ERK-2, but did not affect Jun kinase tyrosine phosphorylation or kinase activity. In addition, treatment of AGS-B cells with H2O2 resulted in increased c-fos/c-jun mRNA expression and AP-1 activity, and also led to increased phosphorylation of epidermal growth factor receptor (EGFR) and Shc. H2O2-dependent stimulation of HDC promoter activity was completely inhibited by kinase-deficient ERKs, dominant-negative (N17 and N15) Ras, and dominant-negative Raf, and partially blocked by a dominant-negative EGFR mutant. In contrast, protein kinase C blockade did not inhibit H2O2-dependent induction of the HDC promoter. Finally, deletion analysis demonstrated that the H2O2 response element could be mapped to the GAS-RE (nucleotides 2 to 24) of the basal HDC promoter. Overall, these studies suggest that oxidant stress activates the HDC promoter through the GAS-RE, and through an Ras-, Raf-, and ERK-dependent pathway at least partially involving the EGFR.
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Affiliation(s)
- M Höcker
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Universitätsklinikum Charité, Campus Virchow Klinikum, Humboldt Universität, Berlin, Germany
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26
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Ahdieh N, Blikslager AT, Bhat BG, Coleman RA, Argenzio RA, Rhoads JM. L-glutamine and transforming growth factor-alpha enhance recovery of monoacylglycerol acyltransferase and diacylglycerol acyltransferase activity in porcine postischemic ileum. Pediatr Res 1998; 43:227-233. [PMID: 9475289 DOI: 10.1203/00006450-199802000-00012] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Recovery of the ability to digest and absorb lipids is essential to the maintenance of normal nutrition in infants with bowel damage. Two intrinsic microsomal enzymes, monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT), catalyze the major pathway for intestinal triacylglycerol biosynthesis. This study describes the effects of intestinal ischemia on epithelial DGAT and MGAT activities and their recovery in response to two luminal treatments: L-glutamine (Gln), the primary intestinal fuel, and transforming growth factor-alpha (TGF-alpha), a mitogenic hormone similar to epidermal growth factor present in breast milk. Ischemic damage and recovery were analyzed in mucosa from Thiry-Vella loops in the mid-ileum of 7-wk-old pigs. Loops were subjected to 2-h occlusion of local mesenteric arteries, followed by 6 or 72 h of recovery in the presence of luminal glucose (control), Gln, or TGF-alpha. Ischemic tissue followed by 6-h recovery exhibited an approximate 50% decrease in both MGAT and DGAT activities compared with nonischemic loop tissue. At 72 h, MGAT and DGAT recovery in Gln plus TGF-alpha-treated loops was significantly greater than their corresponding 6-h peak damage levels (p < 0.05). From 6 to 72 h, MGAT increased 4-fold and DGAT increased 3.6-fold after Gln plus TGF-alpha treatment. With other treatments, MGAT and DGAT activities increased <2.5-fold from 6 to 72 h. This study shows that intestinal MGAT and DGAT activities decrease after ischemic damage, yet recover rapidly in bowel exposed to Gln and/or TGF-alpha. By stimulating the rate of recovery of the villi and lipid synthesizing enzymes, these treatments could improve the efficacy of enteral feeding in infants recovering from bowel damage.
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Affiliation(s)
- N Ahdieh
- Department of Nutrition, Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill 27599-7220, USA
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27
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Matsunaga C, Fujimoto K, Iwakiri R, Koyama T, Ogata S, Gotoh Y, Matsuo S, Sakai T. Lingual factors enhance the increase of ornithine decarboxylase activity in rat jejunal mucosa after feeding. Metabolism 1996; 45:1284-7. [PMID: 8843186 DOI: 10.1016/s0026-0495(96)90249-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Luminal nutrients are the main factors that stimulate ornithine decarboxylase (ODC) activity in rat intestinal mucosa following feeding. The aim of the present study was to determine whether lingual (oral) factors are related to the increase in jejunal ODC activity after feeding. ODC activity in the jejunum and liver was measured 3 hours after refeeding of 48-hour fasted rats. In the first experiment, rats were refed with a regular pellet, powder, or liquid diet. In the second experiment, rats were infused with the liquid diet through a gastric infusion tube following 48 hours' fasting. In the third experiment, the experimental rats had a gastric fistula that allowed free drainage from the stomach of all ingested liquid diet. In the fourth experiment, a truncal vagotomy was performed 1 week before the experiment. The increase of ODC activity in the jejunum of rats fed with the liquid diet was less than that of rats fed with the pellet diet or powder diet. The increase of ODC activity in the jejunal mucosa of rats infused through the gastric tube was less than that of rats fed per os, and the increase of ODC activity in the liver did not differ between these experimental groups. ODC activity did not increase in rats with a gastric fistula. Vagotomy did not affect the increase of jejunal ODC activity after feeding. In conclusion, the increase of ODC activity after feeding was attenuated in rats in which the diet was given by bypassing the mouth. This indicates that lingual factors enhance the increase of ODC activity in the jejunal mucosa after feeding, but the lingual factors alone do not increase ODC activity in the jejunum.
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Affiliation(s)
- C Matsunaga
- Department of Internal Medicine, Saga Medical School, Japan
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28
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Bischoff SC. Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut. BAILLIERE'S CLINICAL GASTROENTEROLOGY 1996; 10:443-59. [PMID: 8905118 DOI: 10.1016/s0950-3528(96)90052-4] [Citation(s) in RCA: 49] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Despite the progress made in understanding the mechanisms of allergic disease, the pathophysiology and clinical significance of intestinal allergic reactions is largely unclear. The intestinal mucosa is pre-destined for allergic reactions against food proteins and other antigens, and a number of studies indicate that allergic reactions occur in the GI tract. However, only a few epidemiological data are available, and the mechanisms are poorly understood. Intestinal allergic reactions may be different to classical IgE-mediated reactions because patients with intestinal allergy often have negative skin tests and low levels of serum IgE. There is increasing evidence that, as with the findings in the skin and lung, mast cells and eosinophils play a central role in mediating intestinal allergic reactions. Furthermore, both types of cell are found to be activated in a number of other GI inflammatory diseases such as inflammatory bowel disease, celiac disease and eosinophilic gastroenteritis. However, the relationship between these pathologies and intestinal allergy is largely unclear. A major clinical problem is the lack of appropriate means for confirming the diagnosis of intestinal allergy. However, new test systems have been developed--such as the measurement of eosinophil mediators in stool samples or endoscopic provocation tests performed locally at the intestinal mucosa, which may improve the possibility of identifying afflicted patients on an objective basis. Since symptoms of intestinal allergic reactions are variable and non-specific, the diagnosis requires the use of multiple tests and the exclusion of other pathologies such as infectious disease or non-immunological intolerance reactions. The preferred therapeutic option is avoidance of the allergens of relevance; however, this approach can be realized only in some patients, whereas others require additional treatment, for example, with oral cromoglycate or corticosteroids. Although we do not yet know to what extent intestinal allergic reactions may be an aetiological factor in GI diseases, such reactions should be considered in the differential diagnosis of unclear intestinal inflammation and irritable bowel syndrome.
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Affiliation(s)
- S C Bischoff
- Division of Gastroenterology and Hepatology, Medical School of Hannover, Germany
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Zhang Z, Höcker M, Koh TJ, Wang TC. The Human Histidine Decarboxylase Promoter Is Regulated by Gastrin and Phorbol 12-Myristate 13-Acetate through a Downstream -Acting Element. J Biol Chem 1996. [DOI: 10.1074/jbc.271.24.14188] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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30
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Morita H, Fujimoto K, Sakata T, Kurokawa M, Yoshimatsu H, Noda T, Iwakiri R, Sakai T. Ornithine decarboxylase activity in rat intestinal mucosa and liver is stimulated by central administration of 2-deoxy-D-glucose but not of 2,5-anhydro-D-mannitol. Brain Res 1996; 719:112-6. [PMID: 8782870 DOI: 10.1016/0006-8993(96)00138-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
It has been shown that 2-deoxy-D-glucose (2-DG) inhibits glucose utilization and elicits feeding through the lateral hypothalamus. In contrast, 2,5-anhydro-D-mannitol (2,5-AM), blocking glycogenolysis and/or gluconeogenesis, elicits feeding through the ventromedial hypothalamus. The aim of the present study was to determine whether ornithine decarboxylase (ODC) activity in the rat small intestine is stimulated by infusion into the third ventricle of 2-DG or of 2,5-AM. Under anesthesia, a cannula was implanted into the third ventricle one week before the experiment. Each rat was infused with 6, 12, and 24 mumol 2-DG or 2,5-AM into the third ventricle without disturbing the behavior. Ingestive behavior was observed for one h after the infusion. ODC activity in the intestinal mucosa and the liver was measured 2 h after the infusion. Additionally, ODC activity was measured in vagotomized rats. Both test solutions elicit feeding at 24 mumol/rat. Infusion of 2-DG into the cerebroventricle significantly increased ODC activity in the duodenal and jejunal mucosa and the liver. In contrast to 2-DG, infusion of 2,5-AM did not increase ODC activity in the intestinal mucosa or liver. Truncal vagotomy attenuated the increase of ODC activity in the intestinal mucosa and liver induced by 2-DG. The present study showed that 2-DG, but not 2,5-AM, increased ODC activity in the peripheral organs, indicating that glucose-metabolism at specific sites of the central nervous system, including the lateral hypothalamus, is important for stimulatory signals to ODC activity. It is also indicated that the stimulatory signals from the central nervous system are mediated, at least in part, via the efferent vagal nerve.
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Affiliation(s)
- H Morita
- Department of Internal Medicine, Saga Medical School, Japan
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31
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Valen G, Kaszaki J, Szabo I, Nagy S, Vaage J. Activity of histamine metabolizing and catabolizing enzymes during reperfusion of isolated, globally ischemic rat hearts. Inflamm Res 1996; 45:145-9. [PMID: 8689395 DOI: 10.1007/bf02265169] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Myocardial ischemia-reperfusion injury increases both tissue levels and release of histamine. To study the possible effects of ischemia-reperfusion on histamine metabolism tissue activities of histidine decarboxylase (HDC), histamine N-methyl transferase (HNMT) and diamine oxidase (DAO) were investigated in isolated rat hearts subjected to either 20 min global ischemia and 40 min reperfusion (n = 10) or control perfusion (n = 8). Histamine in the coronary effluent increased from 21 +/- 4 nmol/min (mean +/- SEM) before ischemia to 55 +/- 5 and 50 +/- 7 nmol/min after 4 and 10 min reperfusion (p < 0.004 and p < 0.004). Tissue HDC activity did not change during observation in any group. HNMT activity was unchanged in controls, but increased from 0.37 +/- 0.04 to 0.84 +/- 0.18 and 0.96 +/- 0.22 pmol methylhistamine/mg protein hour after 4 and 10 min reperfusion (p < 0.008 and p < 0.01). DAO decreased similarly in controls and ischemic-reperfused hearts during observation. In conclusion, the previously observed increase of tissue histamine during reperfusion cannot be explained by increased histamine synthesis or decreased histamine catabolism.
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Affiliation(s)
- G Valen
- Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden
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32
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Bischoff SC, Schwengberg S, Wordelmann K, Weimann A, Raab R, Manns MP. Effect of c-kit ligand, stem cell factor, on mediator release by human intestinal mast cells isolated from patients with inflammatory bowel disease and controls. Gut 1996; 38:104-14. [PMID: 8566835 PMCID: PMC1382987 DOI: 10.1136/gut.38.1.104] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The regulation of mediator release in human intestinal mast cells is largely unknown. Apart from IgE receptor crosslinking no secretagogues have been described so far. This study examined the effect of two cytokines (c-kit ligand and interleukin 3) and other agonists on human intestinal mast cell function. Cells were isolated from surgery specimens of 47 patients undergoing intestinal resection because of tumours or inflammatory bowel disease. Cell suspensions contained 3.6% mast cells (mean of 50 experiments). After preincubation without or with c-kit ligand or interleukin 3, cells were stimulated by IgE receptor crosslinking, C5a or formyl-methionyl-leucyl-phenylalanine (fMLP). Histamine and sulphidoleukotriene release was measured in supernatants. The sequential stimulation of the cells with c-kit ligand and IgE receptor crosslinking induced the release of high amounts of histamine and leukotrienes, whereas each agonist by itself induced only marginal mediator release. Interleukin 3 induced no release by itself, but enhanced the IgE receptor dependent release, possibly by an indirect mechanism. No significant mediator release was seen in response to C5a and fMLP, even if the cells were pretreated with c-kit ligand. The mediator release, particularly that of leukotrienes, was higher in cells isolated from actively inflamed tissue from patients with inflammatory bowel disease compared with controls. In conclusion, it was found that, apart from IgE receptor crosslinking, c-kit ligand and interleukin 3 regulate mediator release in human intestinal mast cells. The enhancement of mediator release by cytokines may be of particular relevance in the pathogenesis of inflammatory bowel diseases and food intolerance reactions.
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Affiliation(s)
- S C Bischoff
- Department of Gastroenterology and Hepatology, Medical School of Hannover, Germany
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Höcker M, Zhang Z, Koh TJ, Wang TC. The regulation of histidine decarboxylase gene expression. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 1996; 69:21-33. [PMID: 9041686 PMCID: PMC2588973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Histamine is a biogenic amine, which is involved in a variety of biologic processes comprising inflammation, allergic responses, neurotransmission and regulation of gastric acid secretion. The key enzyme for the generation of histamine is histidine decarboxylase (HDC), which converts the amino acid L-histidine to histamine. In this article, we review the history, biochemistry and molecular biology of this enzyme. Northern blot studies in rats demonstrated that HDC gene expression in the stomach and liver are developmentally regulated with highest levels of expression in the late fetal state, indicating a role of the gene in growth and development. In the stomach of adult rats, HDC mRNA levels are elevated after omeprazole-induced hypergastrinemia, and in situ hybridization showed that expression of HDC is restricted to the glandular area in which ECL cells are located. Since no permanent ECL cell line is at hand for in vitro studies, we established a suitable cell system by stable transfection of a human gastric adenocarcinoma cell line (AGS) with the CCK-B/gastrin receptor. Transfection of this AGS-B cell line with reporter gene constructs comprising 5'-flanking DNA sequence of the HDC gene joined to the firefly luciferase gene revealed transcriptional regulation of the HDC promoter by gastrin through a protein-kinase C-dependent pathway. Taken together, these studies are consistent with the concept of HDC transcriptional regulation as at least one phase of the overall response to gastrin.
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Affiliation(s)
- M Höcker
- Gastrointestinal Unit, Massachusetts General Hospital, Boston 02114, USA
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Fujimoto K, Gotoh Y, Ogata S, Tsunada S, Ohyama T, Ootani A, Okamoto K, Sakata T. Histaminergic control of mucosal repair in the small intestine. OBESITY RESEARCH 1995; 3 Suppl 5:795S-799S. [PMID: 8653565 DOI: 10.1002/j.1550-8528.1995.tb00502.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The aim of the present paper was to summarize histamine-mediated repair of rat intestinal mucosa. To evaluate intestinal repair, we examined lipid transport (an index of intestinal mucosal function) after 15 minutes occlusion of the superior mesenteric artery. Rats were pretreated with alpha-fluoromethylhistidine (a suicide inhibitor of histidine decarboxylase, a synthesizing enzyme of histamine), H1-receptor antagonist (chlorpheniramine maleate), H2-antagonist (cimetidine), or H3-antagonist (thioperamide) before ischemia-reperfusion (I/R). Lipid transport to rat mesenteric lymph decreased significantly 24 hours after I/R in all groups tested compared to sham-treated rats. Lipid transport was restored 48 hours after I/R in the vehicle-pretreated control group. Lipid transport was not restored to the control level 48 hours after I/R in rats pretreated with H1-antagonist and a suicide inhibitor of histidine decarboxylase. In contrast, intestinal function was restored to the control level 48 hours after I/R in rats pretreated with H2- and H3-antagonists. These results support our previous findings that newly formed histamine after I/R plays an important role in mucosal recovery through H1-receptors.
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Affiliation(s)
- K Fujimoto
- Department of Internal Medicine, Saga Medical School, Japan
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Stimulatory signals from the central nervous system for ornithine decarboxylase activity in the rat duodenal mucosa. PATHOPHYSIOLOGY 1995. [DOI: 10.1016/0928-4680(95)00005-l] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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36
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Fujimoto K, Sakata Y, Tsunada S, Koyama T, Morita H, Ogata S, Matsunaga C, Gotoh Y, Iwakiri R. Newly synthesized histamine accelerates ornithine decarboxylase activity in rat intestinal mucosa after ischemia-reperfusion. Dig Dis Sci 1995; 40:717-21. [PMID: 7720459 DOI: 10.1007/bf02064967] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
We previously demonstrated that both histamine synthesis (histidine decarboxylase activity) and polyamine synthesis (ornithine decarboxylase activity) increased in the rat intestinal mucosa after ischemia-reperfusion, whereas the relationship between these two factors remains unclear. To elucidate this relationship, we performed the present study. The superior mesenteric artery was occluded for 15 min followed by reperfusion. After ischemia-reperfusion, histidine decarboxylase activity and ornithine decarboxylase activity in the rat jejunal mucosa were measured in a time-dependent manner. Histidine decarboxylase activity increased 1 hr after ischemia-reperfusion, although ornithine decarboxylase activity did not; however, its activity did increase 6 hr after. The increase of ornithine decarboxylase activity was attenuated when the increase of histamine synthesis was suppressed by the inhibition of histidine decarboxylase activity caused by pretreatment with alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase. Pretreatment with H1-receptor antagonist attenuated the increase of ornithine decarboxylase activity after ischemia-reperfusion. These results indicate that the newly synthesized histamine, as indicated by an increase of histidine decarboxylase activity, increases ornithine decarboxylase activity after ischemia-reperfusion of the rat intestinal mucosa.
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Affiliation(s)
- K Fujimoto
- Department of Internal Medicine, Saga Medical School, Japan
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Tsunada S, Fujimoto K, Gotoh Y, Sakai T, Kang M, Sakata T, Granger DN, Tso P. Role of histamine receptors in intestinal repair after ischemia-reperfusion in rats. Gastroenterology 1994; 107:1297-304. [PMID: 7523223 DOI: 10.1016/0016-5085(94)90530-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND/AIMS Previously, we showed that an elevated production of histamine promotes the healing of injured intestinal mucosa after ischemia-reperfusion. The aim of the present study was to determine whether histamine-mediated repair of the intestinal mucosa after ischemia-reperfusion involves the engagement of H1 or H2 receptors. METHODS The superior mesenteric artery was occluded for 15 minutes followed by reperfusion, and H1- or H2-receptor antagonists were infused intraduodenally. After ischemia-reperfusion, ornithine decarboxylase activity in the jejunal mucosa and lipid transport to mesenteric lymph were examined. RESULTS In jejunal mucosa, ornithine decarboxylase activity markedly increased at 6 hours after reperfusion and remained elevated at 48 hours. The ischemia-reperfusion-induced increase in ornithine decarboxylase activity was attenuated (in a dose-dependent manner) by an H1-receptor antagonist (chlorpheniramine maleate) but not by an H2 antagonist (cimetidine). Intraperitoneal injection of an H3 antagonist (thioperamide) increased histamine output in mesenteric lymph and stimulated intestinal ornithine decarboxylase activity. Transport of dietary lipid into mesenteric lymph was depressed 24 hours after an ischemic insult, yet it returned to the normal level 48 hours after ischemia-reperfusion. The recovery of the lipid transport normally observed at 48 hours after ischemia-reperfusion was attenuated by the H1 antagonist. CONCLUSIONS The beneficial effects of histamine on the repair of intestinal mucosa after ischemia-reperfusion results from the engagement and activation of the H1 receptor.
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Affiliation(s)
- S Tsunada
- Department of Internal Medicine, Saga Medical School, Nabeshima, Japan
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Yoshimatsu H, Machidori H, Doi T, Kurokawa M, Ookuma K, Kang M, Fujimoto K, Sakata T. Abnormalities in obese Zuckers: defective control of histaminergic functions. Physiol Behav 1993; 54:487-91. [PMID: 8415942 DOI: 10.1016/0031-9384(93)90240-g] [Citation(s) in RCA: 29] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Histaminergic functions in the hypothalamus of Zucker obese rats were investigated. Blockade of postsynaptic H1-receptor after infusion of chlorpheniramine into the third cerebroventricle (ICV) failed to affect feeding in obese Zuckers, although feeding was potently elicited in Wistar King A control rats. Presynaptic increase in histamine by an H3-receptor antagonist, thioperamide, suppressed feeding in Wistar controls, but not in obese Zuckers. Under high ambient temperature, Wistar controls decreased food intake and maintained their rectal temperature normally. However, obese Zuckers and histamine depleted rats due to alpha-fluoromethyl-histidine (FMH), a specific "suicide" inhibitor of a histamine synthesizing decarboxylase enzyme (HDC), failed to show this decrease in food intake as adaptive behavior. Their rectal temperature concomitantly elevated in response to heated circumstance. ICV infusion of thioperamide increased the blood glucose level in Wistar controls, but not in obese Zuckers. The defect in all these regulatory functions found in obese Zuckers may be derived from an excessive decrease in hypothalamic histamine content due to inactivity of HDC. The histamine-depleted model sufficiently mimicked the abnormalities in obese Zuckers.
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Affiliation(s)
- H Yoshimatsu
- Department of Internal Medicine I, Oita Medical University, Japan
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Mori H, Iwakiri R, Tanaka J, Hirano M, Koyama T, Sakata H, Fujimoto K. Subdiaphragmatic vagotomy abolishes increase in ornithine decarboxylase activity of rat duodenal mucosa after ischemia-reperfusion in superior mesenteric artery. GASTROENTEROLOGIA JAPONICA 1993; 28:505-10. [PMID: 8375623 DOI: 10.1007/bf02776948] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
In order to evaluate the systemic and neural factors on ornithine decarboxylase (ODC) activity of rat intestinal mucosa, ODC activity in duodenal mucosa, where blood flow did not decrease by superior mesenteric artery (SMA) occlusion, was compared to that of jejunal and ileal mucosa, where blood flow decreased to 90% of the initial value after SMA occlusion. Rats were allowed to recover after SMA occlusion before harvesting intestinal mucosa for measuring ODC activity. ODC activity in the jejunum and the ileum increased markedly 6 h after ischemia-reperfusion (I/R) and more than 72 h were required for ODC activity to return to normal. ODC activity in the duodenum did not change until 24 h after I/R, but the activity increased 48 h after I/R, and this increase continued for 2 days. Subdiaphragmatic vagotomy completely abolished the increase in ODC activity in the duodenum, whereas the same procedure had no influence on ODC activity in the jejunum or the ileum. These results indicate that a neural signal from the central nervous system via the efferent vagal nerve following I/R was an important factor in the increase in ODC activity of duodenal mucosa, where blood flow was not influenced by SMA occlusion.
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Affiliation(s)
- H Mori
- Department of Internal Medicine, Saga Medical School, Japan
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Fujiskai J, Fujimoto K, Oohara A, Sakata T, Hirano M, Ohyama T, Iwakiri R, Yamaguchi M. Roles of histamine and diamine oxidase in mucosa of rat small intestine after ischemia-reperfusion. Dig Dis Sci 1993; 38:1195-200. [PMID: 8325182 DOI: 10.1007/bf01296067] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
To examine the roles of histamine and diamine oxidase in the intestine after ischemia-reperfusion, we measured histamine content, diamine oxidase activity, and ornithine decarboxylase activity in rat intestinal mucosa 6 hr following various periods of ischemia. In addition, mortality rates of rats after various periods of ischemia were observed. The superior mesenteric artery was occluded for 15, 30, or 60 min. Ornithine decarboxylase activity increased in the 15-, 30-, and 60-min ischemic groups compared to the sham-operated control group. In the prolonged ischemic group (60-min ischemia), both histamine concentration and diamine oxidase activity in the mucosa decreased, contributing to an increase in circulating histamine. In the 60-min ischemic group, the mortality rate of rats was 25%, which was significantly larger than the control groups. Pretreatment with aminoguanidine, which suppressed diamine oxidase activity, increased the mortality rate. These results indicate that histamine released from the intestinal mucosa has a harmful effect on rats, and diamine oxidase activity plays an important role when the small intestine is subjected to prolonged period of ischemia.
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Affiliation(s)
- J Fujiskai
- Department of Internal Medicine, Saga Medical School, Japan
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