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Kim MJ, Kim SY, Kim JD, Park M, Kim YH, Kim KW, Sohn MH. Release of sputum neutrophil granules is associated with pulmonary function and disease severity in childhood asthma. BMC Pulm Med 2024; 24:532. [PMID: 39448961 PMCID: PMC11515414 DOI: 10.1186/s12890-024-03340-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 10/10/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Myeloperoxidase (MPO) and human neutrophil lipocalin or neutrophil gelatinase-associated lipocalin (HNL/NGAL) are stored in neutrophil granulocytes and secreted upon activation of the cells. They have been proposed to reflect the degree of inflammation in the airways. However, their role as potential markers of disease severity in childhood asthma remains unknown. This study investigated the relationship between the expression of MPO and HNL/NGAL and childhood asthma. METHODS A total of 83 pediatric patients with asthma and 59 controls were enrolled. Using enzyme-linked immunosorbent assays, the human MPO and HNL/NGAL levels were measured in sputum supernatants. Assessments including spirometry, methacholine challenge test, and atopy test were conducted. RESULTS No difference in sputum neutrophil counts was observed between pediatric patients with asthma and controls. However, sputum MPO and HNL/NGAL levels were significantly higher in patients with asthma than in controls (p = 0.021 and p < 0.001, respectively), especially in patients with moderate-to-severe persistent asthma. In patients with asthma, sputum MPO and HNL/NGAL levels showed a positive correlation with sputum neutrophil counts (MPO, r = 0.433, p < 0.001; HNL/NGAL, r = 0.584, p < 0.001) and with each other (r = 0.628, p < 0.001). Moreover, sputum HNL/NGAL level demonstrated better ability to accurately reflect current pulmonary function, airway inflammation, and limitations than MPO level in this study. CONCLUSIONS Sputum MPO and HNL/NGAL levels, which reflect neutrophil activation in airways, were increased in pediatric patients with asthma. Moreover, sputum MPO and HNL/NGAL may serve as appropriate assessment indicators of asthma severity in pediatric patients.
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Affiliation(s)
- Min Jung Kim
- Department of Pediatrics, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin- si, Gyeonggi-do, Korea
| | - Soo Yeon Kim
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-gu, Seoul, 03722, Korea
| | - Jong Deok Kim
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-gu, Seoul, 03722, Korea
| | - Mireu Park
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-gu, Seoul, 03722, Korea
| | - Yoon Hee Kim
- Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Won Kim
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-gu, Seoul, 03722, Korea
| | - Myung Hyun Sohn
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-gu, Seoul, 03722, Korea.
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Jun YK, Yoon HT, Kwon SH, Jo UH, Kim JE, Han YM, Kim MS, Im JP, Lee DH, Kim JS, Koh SJ, Park H. Regulation of psoriasis, colitis, and the intestinal microbiota by clusterin. Sci Rep 2023; 13:15405. [PMID: 37717073 PMCID: PMC10505212 DOI: 10.1038/s41598-023-42019-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 09/04/2023] [Indexed: 09/18/2023] Open
Abstract
Psoriasis, a chronic and systemic inflammatory disorder characterized by activation of the interleukin (IL)-23/IL-17 axis, may be associated with the intestinal microbiota through the so-called "gut-skin axis." Clusterin is a glycoprotein ubiquitously distributed in mammalian tissues; however, its role in psoriasis is unclear. Therefore, we evaluated the role of clusterin in psoriatic skin inflammation, systemic inflammation, and colitis using a murine model of IMQ-induced psoriasis. In IMQ-treated clusterin-knockout (clusterin-/-) mice, the expressions of inflammatory cytokines in clusterin-silenced human keratinocytes and intestinal microbial composition were analyzed. We also examined clusterin expression in the skin tissues of patients with psoriasis. IMQ-induced psoriatic skin inflammation is suppressed in clusterin-/- mice. Long-term administration of IMQ induced systemic inflammation and colitis; however, both were alleviated by the genetic deletion of clusterin. Genetic silencing of clusterin in human keratinocytes inhibited the production of inflammatory cytokines involved in the initiation and progression of psoriasis. The composition of the intestinal microbiota in IMQ-treated clusterin-/- and wild-type mice was different. Genetic deletion of clusterin suppressed the increase in the Firmicutes/Bacteroidetes (F/B) ratio. Skin tissues of patients with psoriasis showed high clusterin expression. In conclusion, inhibition of clusterin decreased psoriatic skin inflammation, systemic inflammation, colitis, and altered the F/B ratio in an IMQ-induced murine psoriasis model.
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Affiliation(s)
- Yu Kyung Jun
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
| | - Hee Tae Yoon
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
| | - So Hyun Kwon
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
| | - Ui Hyeon Jo
- Department of Dermatology, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Ji Eun Kim
- Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Yoo Min Han
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Min-Seon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Pil Im
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Joo Sung Kim
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea
| | - Seong-Joon Koh
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea.
| | - Hyunsun Park
- Laboratory of Intestinal Mucosa and Skin Immunology, Liver Research Institute and Seoul National University College of Medicine, Seoul, Korea.
- Department of Dermatology, SMG-SNU Boramae Medical Center, Seoul, Korea.
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
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Xepapadaki P, Adachi Y, Pozo Beltrán CF, El-Sayed ZA, Gómez RM, Hossny E, Filipovic I, Le Souef P, Morais-Almeida M, Miligkos M, Nieto A, Phipatanakul W, Pitrez PM, Wang JY, Wong GW, Papadopoulos NG. Utility of biomarkers in the diagnosis and monitoring of asthmatic children. World Allergy Organ J 2022; 16:100727. [PMID: 36601259 PMCID: PMC9791923 DOI: 10.1016/j.waojou.2022.100727] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 11/17/2022] [Accepted: 11/17/2022] [Indexed: 12/23/2022] Open
Abstract
Asthma imposes a heavy morbidity burden during childhood; it affects over 10% of children in Europe and North America and it is estimated to exceed 400 million people worldwide by the year 2025. In clinical practice, diagnosis of asthma in children is mostly based on clinical criteria; nevertheless, assessment of both physiological and pathological processes through biomarkers, support asthma diagnosis, aid monitoring, and further lead to better treatment outcomes and reduced morbidity. Recently, identification and validation of biomarkers in pediatric asthma has emerged as a top priority across leading experts, researchers, and clinicians. Moreover, the implementation of non-invasive biomarkers for the assessment and monitoring of paediatric patients with asthma, has been prioritized; however, only a proportion of them are currently included in the clinical practise. Although, the use of non-invasive biomarkers is highly supported in recent asthma guidelines for documenting diagnosis and supporting monitoring of asthmatic patients, data on the Pediatric population are limited. In the present report, the Pediatric Asthma Committee of the World Allergy Organization (WAO), aims to summarize and discuss available data for the implementation of non-invasive biomarkers in the diagnosis and monitoring in children with asthma. Information on the most studied biomarkers, including spirometry, oscillometry, markers of allergic sensitization, fractional exhaled nitric oxide, and the most recent exhaled breath markers and "omic" approaches, will be reviewed. Practical limitations and considerations based on both experts' opinion and critical review of the literature, on the utility of all "well-known" and newly introduced non-invasive biomarkers will be presented. A critical commentary on biomarkers' use in diagnosing and monitoring asthma during the COVID-19 pandemic, cost and availability of biomarkers in different settings and in developing countries, the differences on the biomarkers use between Primary Practitioners, Pediatricians, and Specialists and their role on the longitudinal aspect of asthma is provided.
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Affiliation(s)
- Paraskevi Xepapadaki
- Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece
- Corresponding author.
| | - Yuichi Adachi
- Department of Pediatrics, Faculty of Medicine, University of Toyam, Japan
| | | | - Zeinab A. El-Sayed
- Pediatric Allergy, Immunology and Rheumatology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt
| | | | - Elham Hossny
- Pediatric Allergy, Immunology and Rheumatology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt
| | - Ivana Filipovic
- University Hospital Center Dr Dragiša Mišović Hospital Pediatric Department, Serbia
| | - Peter Le Souef
- Faculty of Health and Medical Sciences, Dept of Respiratory Medicine, Child and Adolescent Health Service, University of Western Australia, Perth, Australia
| | | | - Michael Miligkos
- Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece
| | - Antonio Nieto
- Pediatric Pulmonology & Allergy Unit Children's. Health Research Institute. Hospital La Fe, 46026, Valencia, Spain
| | - Wanda Phipatanakul
- Pediatric Allergy and Immunology, Boston Children's Hospital, Boston, MA, USA
| | - Paulo M. Pitrez
- School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Jiu-Yao Wang
- Center for Allergy and Clinical Immunology Research, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Gary W.K. Wong
- Department of Paediatrics, The Chinese University of Hong Kong, China
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Using induced sputum method in clinical practice in patients with bronchial asthma. ACTA BIOMEDICA SCIENTIFICA 2022. [DOI: 10.29413/abs.2022-7.5-2.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This article presents an overview of modern statements of the induced sputum method; detailed description of the methods and protocols for taking sputum in adults and children, methods for processing the obtained substance. The paper describes in detail the features of the cellular composition of induced sputum in healthy individuals and in patients with bronchial asthma, emphasizes the importance of the eosinophilia level as a prognostic and diagnostic criterion of asthma and also determines the functions of other induced sputum cells such as neutrophils, macrophages, basophils. The article is illustrated with photographs of sputum microscopy. In addition to sputum cytology, we give accent to the possibility of using other research methods such as an identification of viral and bacterial pathogens, genomics, proteomics, lipidomics, metabolomics, determination of the concentration of various mediators in the sputum supernatant. The paper presents the ideas on biochemical inflammatory markers and remodelling of the respiratory tract in asthma, which can be determined in sputum (C3a anaphylatoxin, clusterin, periostin, eosinophil-derived neurotoxin, folliculin). In addition, we summarize the information on inflammatory phenotypes of bronchial asthma, emphasize their variability and modification depending on the period of the disease, prescribed treatment, intercurrent respiratory infections, and smoking. The article also presents detailed characteristics of eosinophilic, neutrophilic, mixed and small granulocyte phenotypes of bronchial asthma, and describes the most frequent correlations of phenotypes with the severity and course of the disease, with lung function parameters and other indicators. The paper gives an account of the possibilities of using the induced sputum method for a comprehensive assessment of the course, asthma controllability and the effectiveness of drug therapy, as well as for a personalized selection of an antiinflammatory drug considering the inflammatory phenotype.
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Ghosh S, Rihan M, Ahmed S, Pande AH, Sharma SS. Immunomodulatory potential of apolipoproteins and their mimetic peptides in asthma: Current perspective. Respir Med 2022; 204:107007. [DOI: 10.1016/j.rmed.2022.107007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 10/03/2022] [Indexed: 10/31/2022]
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Müller WEG, Wang X, Neufurth M, Schröder HC. Polyphosphate in Antiviral Protection: A Polyanionic Inorganic Polymer in the Fight Against Coronavirus SARS-CoV-2 Infection. PROGRESS IN MOLECULAR AND SUBCELLULAR BIOLOGY 2022; 61:145-189. [PMID: 35697940 DOI: 10.1007/978-3-031-01237-2_7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Polyanions as polymers carrying multiple negative charges have been extensively studied with regard to their potential antiviral activity. Most studies to date focused on organic polyanionic polymers, both natural and synthetic. The inorganic polymer, polyphosphate (polyP), despite the ubiquitous presence of this molecule from bacteria to man, has attracted much less attention. More recently, and accelerated by the search for potential antiviral agents in the fight against the pandemic caused by the coronavirus SARS-CoV-2, it turned out that polyP disrupts the first step of the viral replication cycle, the interaction of the proteins in the virus envelope and in the cell membrane that are involved in the docking process of the virus with the target host cell. Experiments on a molecular level using the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the cellular angiotensin converting enzyme 2 (ACE2) receptor revealed that polyP strongly inhibits the binding reaction through an electrostatic interaction between the negatively charged centers of the polyP molecule and a cationic groove, which is formed by positively charged amino acids on the RBD surface. In addition, it was found that polyP, due to its morphogenetic and energy delivering activities, enhances the antiviral host innate immunity defense of the respiratory epithelium. The underlying mechanisms and envisaged application of polyP in the therapy and prevention of COVID-19 are discussed.
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Affiliation(s)
- Werner E G Müller
- ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
| | - Xiaohong Wang
- ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Meik Neufurth
- ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Heinz C Schröder
- ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
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Gao S, Wang J, Zhang Q, Shu J, Li C, Li H, Lin J. Cytokine antibody array-based analysis of IL-37 treatment effects in asthma. Aging (Albany NY) 2021; 13:21729-21742. [PMID: 34516405 PMCID: PMC8457575 DOI: 10.18632/aging.203515] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/08/2021] [Indexed: 01/16/2023]
Abstract
Asthma is driven by group 2 innate lymphoid cells, antigen-specific CD4+ T helper type 2 cells and their cytokines such as interleukin (IL)-4, IL-5, IL-13. IL-37 is decreased in asthma and negatively related to Th2 cytokines and other pro-inflammatory cytokines. Our study showed that IL-37 level in asthmatic peripheral blood mononuclear cells was lower than in healthy. Further, IL-37 was negatively correlated with exhaled nitric oxide, asthma control test score, atopy and rhinitis history in asthmatics. Then an OVA-induced asthma mice model treated with rhIL-37 was established. An antibody array was employed to uncover altered cytokines induced by IL-37 in mice lung tissue. 20 proteins differentially expressed after rhIL-37 treatment and five of them were validated in asthmatic peripheral blood mononuclear cells. Consistent with cytokine antibody array, CCL3, CCL4, CCL5 decreased after IL-37 administration. While CXCL9 and CXCL13 were no change. We concluded that IL-37 reduce asthmatic symptoms by inhibit pro-inflammatory cytokine such as CCL3, CCL4, CCL5.
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Affiliation(s)
- Shengnan Gao
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China.,Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 10029, China
| | - Jingru Wang
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing 10029, China
| | - Qing Zhang
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China.,Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 10029, China
| | - Jun Shu
- Institute of Clinical Medicine Science, China-Japan Friendship Hospital, Beijing 10029, China
| | - Chunxiao Li
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing 10029, China
| | - Hongwen Li
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing 10029, China
| | - Jiangtao Lin
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China.,Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 10029, China
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Schepler H, Wang X, Neufurth M, Wang S, Schröder HC, Müller WEG. The therapeutic potential of inorganic polyphosphate: A versatile physiological polymer to control coronavirus disease (COVID-19). Theranostics 2021; 11:6193-6213. [PMID: 33995653 PMCID: PMC8120197 DOI: 10.7150/thno.59535] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 03/19/2021] [Indexed: 12/15/2022] Open
Abstract
Rationale: The pandemic caused by the novel coronavirus SARS-CoV-2 is advancing rapidly. In particular, the number of severe courses of the disease is still dramatically high. An efficient drug therapy that helps to improve significantly the fatal combination of damages in the airway epithelia, in the extensive pulmonary microvascularization and finally multiorgan failure, is missing. The physiological, inorganic polymer, polyphosphate (polyP) is a molecule which could prevent the initial phase of the virus life cycle, the attachment of the virus to the target cells, and improve the epithelial integrity as well as the mucus barrier. Results: Surprisingly, polyP matches perfectly with the cationic groove on the RBD. Subsequent binding studies disclosed that polyP, with a physiological chain length of 40 phosphate residues, abolishes the binding propensity of the RBD to the ACE2 receptor. In addition to this first mode of action of polyP, this polymer causes in epithelial cells an increased gene expression of the major mucins in the airways, of MUC5AC and MUC1, as well as a subsequent glycoprotein production. MUC5AC forms a gel-like mucus layer trapping inhaled particles which are then transported out of the airways, while MUC1 constitutes the periciliary liquid layer and supports ciliary beating. As a third mode of action, polyP undergoes enzymatic hydrolysis of the anhydride bonds in the airway system by alkaline phosphatase, releasing metabolic energy. Conclusions: This review summarizes the state of the art of the biotherapeutic potential of the polymer polyP and the findings from basic research and outlines future biomedical applications.
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Affiliation(s)
- Hadrian Schepler
- Department of Dermatology, University Clinic Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
| | - Xiaohong Wang
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany
| | - Meik Neufurth
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany
| | - Shunfeng Wang
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany
| | - Heinz C. Schröder
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany
| | - Werner E. G. Müller
- ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany
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Reduced Expression of Antimicrobial Protein Secretory Leukoprotease Inhibitor and Clusterin in Chronic Rhinosinusitis with Nasal Polyps. J Immunol Res 2021; 2021:1057186. [PMID: 33506054 PMCID: PMC7810533 DOI: 10.1155/2021/1057186] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 12/20/2020] [Accepted: 12/24/2020] [Indexed: 12/13/2022] Open
Abstract
Introduction Antimicrobial peptides and proteins (AMPs) constitute the first line of defense against pathogenic microorganisms in the airway. The association between AMPs and chronic rhinosinusitis with nasal polyps (CRSwNP) requires further investigations. This study is aimed at investigating the expression and regulation of major dysregulated AMPs in the nasal mucosa of CRSwNP. Methods The expression of AMPs was analyzed in nasal tissue from patients with eosinophilic (E) CRSwNP and nonECRSwNP and healthy subjects using RNA sequencing. The 10 most abundant AMPs expressed differentially in CRSwNP patients were verified by real-time PCR, and of these, the expression and regulation of secretory leukoprotease inhibitor (SLPI) and clusterin (CLU) were investigated further. Results The 10 most abundant AMPs expressed differentially in CRSwNP compared to healthy control, regardless of subtypes, included BPIFA1, BPIFB1, BPIFB2, CLU, LTF, LYZ, and SLPI, which were downregulated, and S100A8, S100A9, and HIST1H2BC, which were upregulated. ELISA and immunofluorescence confirmed the decreased expression of SLPI and CLU levels in CRSwNP. SLPI is expressed in both nasal epithelial cells and glandular cells, whereas CLU is mainly expressed in glandular cells. AB/PAS staining further demonstrated that both SLPI and CLU were mainly produced by mucous cells in submucosal glands. Furthermore, the numbers of submucosal glands were significantly decreased in nasal polyp tissue of CRSwNP compared to nasal tissue of controls. SLPI was downregulated by TGF-β1 and IL-4 in cultured nasal tissues in vitro, while CLU expression was inhibited by TGF-β1. Glucocorticoid treatment for 2 weeks significantly increased the expression of all downregulated AMPs, but not LYZ. Additionally, budesonide significantly increased the expression of SLPI and CLU in cultured nasal tissues. Conclusion The expression of major antimicrobial proteins is significantly decreased in nasal tissue of CRSwNP. The expression of SLPI and CLU is correlated with the numbers of submucosal glands and regulated by inflammatory cytokines and glucocorticoids.
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Zhu T, Li S, Wang J, Liu C, Gao L, Zeng Y, Mao R, Cui B, Ji H, Chen Z. Induced sputum metabolomic profiles and oxidative stress are associated with chronic obstructive pulmonary disease (COPD) severity: potential use for predictive, preventive, and personalized medicine. EPMA J 2020; 11:645-659. [PMID: 33235638 PMCID: PMC7680486 DOI: 10.1007/s13167-020-00227-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 10/19/2020] [Indexed: 02/07/2023]
Abstract
Chronic obstructive pulmonary disease (COPD) is a highly heterogeneous disease, and metabolomics plays a hub role in predictive, preventive, and personalized medicine (PPPM) related to COPD. This study thus aimed to reveal the role of induced sputum metabolomics in predicting COPD severity. In this pilot study, a total of 20 COPD patients were included. The induced sputum metabolites were assayed using a liquid chromatography-mass spectrometry (LC-MS/MS) system. Five oxidative stress products (myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH), neutrophil elastase (NE), and 8-iso-PGF2α) in induced sputum were measured by ELISA, and the metabolomic profiles were distinguished by principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA). The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis, and a significant difference in induced sputum metabolomics was observed between moderate and severe COPD. The KEGG analysis revealed that the glycerophospholipid metabolism pathway was downregulated in severe COPD. Due to the critical role of glycerophospholipid metabolism in oxidative stress, significant negative correlations were discovered between glycerophospholipid metabolites and three oxidative stress products (SOD, MPO, and 8-iso-PGF2α). The diagnostic values of SOD, MPO, and 8-iso-PGF2α in induced sputum were found to exhibit high sensitivities and specificities in the prediction of COPD severity. Collectively, this study provides the first identification of the association between induced sputum metabolomic profiles and COPD severity, indicating the potential value of metabolomics in PPPM for COPD management. The study also reveals the correlation between glycerophospholipid metabolites and oxidative stress products and their value for predicting COPD severity. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-020-00227-w.
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Affiliation(s)
- Tao Zhu
- Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 China
| | - Shanqun Li
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China
| | - Jiajia Wang
- Rheumatology Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 China
| | - Chunfang Liu
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China
| | - Lei Gao
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China
| | - Yuzhen Zeng
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China
| | - Ruolin Mao
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China
| | - Bo Cui
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China
| | - Hong Ji
- California National Primate Research Center, and Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616 USA
| | - Zhihong Chen
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China
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11
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Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice. Antioxidants (Basel) 2020; 9:antiox9040295. [PMID: 32244835 PMCID: PMC7222203 DOI: 10.3390/antiox9040295] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 03/23/2020] [Accepted: 03/30/2020] [Indexed: 12/16/2022] Open
Abstract
Sesamol, isolated from sesame seeds (Sesamum indicum), was previously shown to have antioxidative, anti-inflammatory, and anti-tumor effects. Sesamol also inhibited lipopolysaccharide (LPS)-induced pulmonary inflammatory response in rats. However, it remains unclear how sesamol regulates airway inflammation and oxidative stress in asthmatic mice. This study aimed to investigate the efficacy of sesamol on oxidative stress and airway inflammation in asthmatic mice and tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin, and received oral sesamol on days 14 to 27. Furthermore, BEAS-2B human bronchial epithelial cells were treated with sesamol to investigate inflammatory cytokine levels and oxidative responses in vitro. Our results demonstrated that oral sesamol administration significantly suppressed eosinophil infiltration in the lung, airway hyperresponsiveness, and T helper 2 cell-associated (Th2) cytokine expressions in bronchoalveolar lavage fluid and the lungs. Sesamol also significantly increased glutathione expression and reduced malondialdehyde levels in the lungs of asthmatic mice. We also found that sesamol significantly reduced proinflammatory cytokine levels and eotaxin in inflammatory BEAS-2B cells. Moreover, sesamol alleviated reactive oxygen species formation, and suppressed intercellular cell adhesion molecule-1 (ICAM-1) expression, which reduced monocyte cell adherence. We demonstrated that sesamol showed potential as a therapeutic agent for improving asthma.
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Sobeih AA, Behairy OG, Abd Almonaem ER, Mohammad OI, Mn Abdelrahman A. Clusterin in atopic and non-atopic childhood asthma. Scandinavian Journal of Clinical and Laboratory Investigation 2019; 79:368-371. [PMID: 31161800 DOI: 10.1080/00365513.2019.1624976] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Several biomarkers have been studied to diagnose or to detect the phenotype of asthma. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammatory diseases. We aimed to study serum clusterin level in atopic versus non-atopic childhood asthma and its relation to disease severity. This case-control study included 160 children; 120 stable asthmatic children and 40 apparently healthy children. Asthmatic children were further subdivided into atopic and non-atopic. All children were subjected to medical history taking, clinical examination, and laboratory investigations including complete blood count, serum IgE, serum clusterin level and spirometry before and after bronchodilator therapy. In comparison to controls, patients had significantly higher eosinophils count which was higher in atopic than non-atopic group, also serum IgE level was higher in the atopic asthmatics (118.1 ± 16.2 U/ml) than in both the non-atopic asthmatics (81.2 ± 6.1 U/ml) and the controls (76.3 ± 11.6 U/ml). There was statistical significant difference in serum levels of Clusterin which were highest in the atopic group (182.5 ± 33.5 ng/l), followed by the non-atopic patients (127.5 ± 32.5 ng/l) and lowest in the controls (46.09 ± 7.01 ng/l). Moreover, the higher the severity of asthma, the higher was the level of serum clusterin. In conclusion serum level of clusterin was higher in atopic than non-atopic asthmatic children and it increases significantly with increased severity of the disease.
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Affiliation(s)
- Ahmad Ata Sobeih
- Department of Pediatrics, Faculty of Medicine, Benha University , Benha , Egypt
| | - Ola Galal Behairy
- Department of Pediatrics, Faculty of Medicine, Benha University , Benha , Egypt
| | | | | | - Amira Mn Abdelrahman
- Department of Clinical Pathology, Faculty of Medicine, Benha University , Benha , Egypt
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Shen J, Zhao J, Ye QY, Gu XD. Interference of miR-943-3p with secreted frizzled-related proteins4 (SFRP4) in an asthma mouse model. Cell Tissue Res 2019; 378:67-80. [PMID: 31101982 DOI: 10.1007/s00441-019-03026-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 04/01/2019] [Indexed: 01/08/2023]
Abstract
The aim of this study is to investigate the potential roles of miR-943-3p and its target gene secreted frizzled-related proteins4 (SFRP4) in allergic asthma and elucidate its underlying mechanism, which may prompt a new clue about developing novel treatments of this disease. An allergic asthma mouse model was generated by challenging with ovalbumin (OVA); lung pathological features of mice were viewed using H&E staining; thickness of subepithelial fibrosis and smooth muscle was measured using Masson's trichrome staining. Inflammatory cells from bronchoalveolar lavage fluid (BALF) were counted based on Diff-Quik staining and morphometric analysis. Expressions of miR-943-3p, SFRP4 and Wnt signal pathway-associated proteins were detected using RT-PCR or immunoblotting, respectively. SFRP4 was downregulated in the bronchial biopsies of allergic asthma patients and represented a unique intersection between differentially expressed genes (DEGs) and genes in the Wnt signal pathway. Both miR-943-3p upregulation and SFRP4 downregulation were detected in allergic asthma patients and OVA-induced mice. Besides, OVA-induced mice possessed more inflammatory cells in BALF including macrophage (mac), eosinophil (eos), lymphocyte (lym) and neutrophil (neu), higher expression of collagen, β-catenin and c-Myc as well as thicker subepithelial fibrosis and smooth muscle in lung than control mice. In vivo delivery of miR-943-3p agomir worsened these symptoms, while both miR-943-3p antagomir and Ad-SFRP4 administration effectively alleviated this disease. Taken together, miR-943-3p accelerated the progression of airway inflammation and remodeling in allergic asthma via suppressing the activity of SFRP4 through Wnt signaling pathway in asthma patients and OVA-induced mice.
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Affiliation(s)
- Jian Shen
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, No. 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China.
| | - Jun Zhao
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, No. 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China
| | - Qing-Yan Ye
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, No. 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China
| | - Xi-Dong Gu
- Department of Clinical Laboratory, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, China
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Sol IS, Kim YH, Kim SY, Choi SH, Kim HR, Kim KW, Sohn MH. Exhaled breath temperature as a tool for monitoring asthma control after an attack in children. Pediatr Pulmonol 2019; 54:230-236. [PMID: 30609317 DOI: 10.1002/ppul.24225] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 11/05/2018] [Accepted: 11/29/2018] [Indexed: 11/10/2022]
Abstract
BACKGROUND Exhaled breath temperature (EBT) has been suggested as a non-invasive marker of airway inflammation in asthma. There have been no studies examining longitudinal changes in EBT following asthma attacks. OBJECTIVE To investigate changes in EBT during and after an asthma attack and to relate these changes to changes in respiratory physiological measurements. METHODS We evaluated 38 hospitalized children aged 5-18 years diagnosed with an asthma attack. Spirometry was performed upon hospitalization. During hospitalization, EBT, peak expiratory flow rate (PEFR), and asthma score were measured daily. These tests were repeated 1 week and 1 month after discharge. The overall PEFR change, temporal changes in plateau values at the end of expiration, and time-dynamic associations were evaluated using linear mixed models. RESULTS FEV1 was lower at admission than at discharge (63.3 ± 24 vs 99.5 ± 14 percent of predicted, P < 0.001). The EBT was higher at admission than at 1 week after discharge (34.1°C [range: 33.9-34.8°C] vs 33.6°C [range: 33.0-34.2°C], P = 0.007); overall, EBTs decreased over time (P = 0.007). Among individual subjects, decreased EBT was correlated with increased PEFR over time. Furthermore, plateau values at the end of expiration had a time-dependent, dynamic association with the PEFR during hospitalization (P = 0.005) and between asthma attack onset and asthma status stabilization (P = 0.032). CONCLUSIONS The EBT was elevated during asthma attacks and gradually decreased until asthma was well controlled. The EBT may be a useful, non-invasive tool for monitoring asthma control in children.
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Affiliation(s)
- In Suk Sol
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Hee Kim
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Yeon Kim
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Sun Ha Choi
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Ran Kim
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Kyung Won Kim
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Myung Hyun Sohn
- Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
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Bae CH, Na HG, Choi YS, Song SY, Kim YD. Clusterin Induces MUC5AC Expression via Activation of NF-κB in Human Airway Epithelial Cells. Clin Exp Otorhinolaryngol 2018; 11:124-132. [PMID: 29316784 PMCID: PMC5951062 DOI: 10.21053/ceo.2017.00493] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Revised: 10/08/2017] [Accepted: 11/10/2017] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES Clusterin (CLU) is known as apolipoprotein J, and has three isoforms with different biological functions. CLU is associated with various diseases such as Alzheimer disease, atherosclerosis, and some malignancies. Recent studies report an association of CLU with inflammation and immune response in inflammatory airway diseases. However, the effect of CLU on mucin secretion of airway epithelial cells has not yet been understood. Therefore, the effect and brief signaling pathway of CLU on MUC5AC (as a major secreted mucin) expression were investigated in human airway epithelial cells. METHODS In the tissues of nasal polyp and normal inferior turbinate, the presence of MUC5AC and CLU was investigated using immunohistochemical stain and Western blot analysis. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway of CLU on MUC5AC expression were investigated using immunohistochemical stain, reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and Western blot analysis. RESULTS In the nasal polyps, MUC5AC and CLU were abundantly present in the epithelium on immunohistochemical stain, and nuclear CLU (nCLU) was strongly detected on Western blot analysis. In human NCI-H292 airway epithelial cells or the primary cultures of normal nasal epithelial cells, recombinant nCLU increased MUC5AC expression, and significantly activated phosphorylation of NF-κB. And BAY 11-7085 (a specific NF-κB inhibitor) and knockdown of NF-κB by NF-κB siRNA (small interfering RNA) significantly attenuated recombinant nCLU-induced MUC5AC expression. CONCLUSION These results suggest that nCLU induces MUC5AC expression via the activation of NF-κB signaling pathway in human airway epithelial cells.
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Affiliation(s)
- Chang Hoon Bae
- Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Hyung Gyun Na
- Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Yoon Seok Choi
- Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Si-Youn Song
- Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Yong-Dae Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea
- Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Korea
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Role of clusterin/progranulin in toluene diisocyanate-induced occupational asthma. Exp Mol Med 2018; 50:1-10. [PMID: 29717106 PMCID: PMC5938014 DOI: 10.1038/s12276-018-0085-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 02/13/2018] [Accepted: 03/05/2018] [Indexed: 12/25/2022] Open
Abstract
Toluene diisocyanate (TDI) exposure induces oxidative stress and epithelial cell-derived inflammation, which affect the pathogenesis of TDI-induced occupational asthma (TDI-OA). Recent studies suggested a role for clusterin (CLU) and progranulin (PGRN) in oxidative stress-mediated airway inflammation. To evaluate CLU and PGRN involvement in airway inflammation in TDI-OA, we measured their serum levels in patients with TDI-OA, asymptomatic exposed controls (AECs), and unexposed healthy normal controls (NCs). Serum CLU and PGRN levels were significantly lower in the TDI-OA group than in the AEC and NC groups (P < 0.05). The sensitivity and specificity for predicting the TDI-OA phenotype were 72.4% and 53.4% when either CLU or PGRN levels were below the cutoff values (≤125 μg/mL and ≤68.4 ng/mL, respectively). If both parameters were below the cutoff levels, the sensitivity and specificity were 58.6% and 89.8%, respectively. To investigate CLU and PGRN function, we evaluated their production by human airway epithelial cells (HAECs) in response to TDI exposure and co-culturing with neutrophils. TDI-human serum albumin stimulation induced significant CLU/PGRN release from HAECs in a dose-dependent manner, which positively correlated with IL-8 and folliculin levels. Co-culturing with neutrophils significantly decreased CLU/PGRN production by HAECs. Intracellular ROS production in epithelial cells co-cultured with neutrophils tended to increase initially, but the ROS production decreased gradually at a higher ratio of neutrophils. Our results suggest that CLU and PGRN may be involved in TDI-OA pathogenesis by protecting against TDI-induced oxidative stress-mediated inflammation. The combined CLU/PGRN serum level may be used as a potential serological marker for identifying patients with TDI-OA among TDI-exposed workers.
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Roberts G, Boyle R, Crane J, Hogan SP, Saglani S, Wickman M, Woodfolk JA. Developments in the field of allergy in 2016 through the eyes of Clinical and Experimental Allergy. Clin Exp Allergy 2017; 47:1512-1525. [PMID: 29068551 DOI: 10.1111/cea.13049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2016. Experimental models of allergic disease, basic mechanisms, clinical mechanisms, allergens, asthma and rhinitis, and clinical allergy are all covered.
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Affiliation(s)
- G Roberts
- Clinical and Experimental Sciences and Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.,NIHR Southampton Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.,The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, UK
| | - R Boyle
- Department of Paediatrics, Imperial College London, London, UK
| | - J Crane
- Department of Medicine, University of Otago Wellington, Wellington, New Zealand
| | - S P Hogan
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - S Saglani
- National Heart & Lung Institute, Imperial College London, London, UK
| | - M Wickman
- Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | - J A Woodfolk
- Division of Asthma, Allergy and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
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Zhu LY, Ni ZH, Luo XM, Wang XB. Advance of antioxidants in asthma treatment. World J Respirol 2017; 7:17-28. [DOI: 10.5320/wjr.v7.i1.17] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 11/23/2016] [Accepted: 01/14/2017] [Indexed: 02/07/2023] Open
Abstract
Asthma is an allergic disease, characterized as a recurrent airflow limitation, airway hyperreactivity, and chronic inflammation, involving a variety of cells and cytokines. Reactive oxygen species have been proven to play an important role in asthma. The pathogenesis of oxidative stress in asthma involves an imbalance between oxidant and antioxidant systems that is caused by environment pollutants or endogenous reactive oxygen species from inflammation cells. There is growing evidence that antioxidant treatments that include vitamins and food supplements have been shown to ameliorate this oxidative stress while improving the symptoms and decreasing the severity of asthma. In this review, we summarize recent studies that are related to the mechanisms and biomarkers of oxidative stress, antioxidant treatments in asthma.
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Kim MJ, Lee HS, Sol IS, Kim MN, Hong JY, Lee KE, Kim YH, Kim KW, Sohn MH, Kim KE. Sputum pentraxin 3 as a candidate to assess airway inflammation and remodeling in childhood asthma. Medicine (Baltimore) 2016; 95:e5677. [PMID: 28002338 PMCID: PMC5181822 DOI: 10.1097/md.0000000000005677] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Pentraxin 3 (PTX3) is a soluble pattern recognition receptor and an acute-phase protein. It has gained attention as a new biomarker reflecting tissue inflammation and damage in a variety of diseases. Aim of this study is to investigate the role of PTX3 in childhood asthma.In total, 260 children (140 patients with asthma and 120 controls) were enrolled. PTX3 levels were measured in sputum supernatants using enzyme-linked immunosorbent assay test. We performed spirometry and methacholine challenge tests and measured the total eosinophil count and the serum levels of total IgE and eosinophil cationic protein (ECP) in all subjects.Sputum PTX3 concentration was significantly higher in children with asthma than in control subjects (P < 0.001). Furthermore, sputum PTX3 levels correlated with atopic status and disease severity among patients with asthma. A positive significant correlation was found between sputum PTX3 and the bronchodilator response (r = 0.25, P = 0.013). Sputum PTX3 levels were negatively correlated with forced expiratory volume in 1 second (FEV1) (r = -0.30, P = 0.001), FEV1/forced vital capacity (FVC) (r = -0.27, P = 0.002), and FEF25-75 (r = -0.392, P < 0.001), which are indicators of airway obstruction and inflammation. In addition, the PTX3 concentration in sputum showed negative correlations with post-bronchodilator (BD) FEV1 (r = -0.25, P < 0.001) and post-BD FEV1/FVC (r = -0.25, P < 0.001), which are parameters of persistent airflow limitation reflecting airway remodeling.Sputum PTX3 levels increased in children with asthma, suggesting that PTX3 in sputum could be a candidate molecule to evaluate airway inflammation and remodeling in childhood asthma.
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