Research Report
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World J Gastroenterol. Nov 7, 2014; 20(41): 15327-15334
Published online Nov 7, 2014. doi: 10.3748/wjg.v20.i41.15327
Intestinal ischemia-reperfusion of macaques triggers a strong innate immune response
Hao Wu, Yi-Yun Deng, Ling Liu, Qing-Hua Tan, Chun-Hui Wang, Mei-Mei Guo, Yong-Mei Xie, Cheng-Wei Tang
Hao Wu, Ling Liu, Qing-Hua Tan, Chun-Hui Wang, Cheng-Wei Tang, Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Yi-Yun Deng, Department of Intensive Care Unit, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Mei-Mei Guo, Yong-Mei Xie, Laboratory Peptides Related to Human Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Wu H and Deng YY contributed equally to this work; Tang CW designed the research and revised the manuscript; Wu H, Liu L, Tan QH, Wang CH, Guo MM, Xie YM performed the research; Wu H and Deng YY wrote the paper and analyzed the data.
Supported by Key Grant of the Natural Science Fund of China, No. 30330270; Chengdu Bureau of Science and Technology Research Projects, No. 11DXYB352SF; Chengdu Bureau of Science and Technology Research Projects, No. 12PPYB080SF-002
Correspondence to: Cheng-Wei Tang, MD, PhD, Department of Gastroenterology, West China Hospital, Sichuan University, Guoxue Xiang 37, Chengdu 610041, Sichuan Province, China. cwtang@medmail.com.cn
Telephone: +86-28-85423887 Fax: +86-28-85423887
Received: March 12, 2014
Revised: May 8, 2014
Accepted: June 13, 2014
Published online: November 7, 2014
Processing time: 243 Days and 0.7 Hours
Abstract

AIM: To investigate inflammatory injury in the intestinal mucosa after intestinal ischemia-reperfusion (IIR) with Toll-like receptor (TLR)-mediated innate immunity.

METHODS: Ten macaques were randomized into control and IIR groups. The distribution and expression level of TLR2, TLR4, MD2, nuclear factor (NF)-κB p65 and interferon (IFN)-γ were measured by immunohistochemical stain and western blotting. The mRNA expression of TLR4, TLR2, MD2, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured by reverse transcriptase-polymerase chain reaction. The cytokine levels in blood and intestinal tissues were measured by ELISA.

RESULTS: Obvious hemorrhage and erosion of mucosae were seen in the IIR group. Expression of TLR2, TLR4, MD2, NF-κB p65 and IFN-γ was significantly higher in the IIR group than in the control group (0.13 ± 0.04, 0.22 ± 0.04, 0.16 ± 0.06, 0.65 ± 0.12, 0.38 ± 0.10 vs 0.07 ± 0.04, 0.08 ± 0.03, 0.04 ± 0.02, 0.19 ± 0.06, 0.14 ± 0.05, P < 0.05). In addition, the expression of TLR2, TLR4, MD2, IL-1β and TNF-α mRNA in the IIR group were significantly higher than those of control group(1.52 ± 0.15, 1.39 ± 0.06, 1.94 ± 0.12, 1.48 ± 0.15, 0.66 ± 0.08 vs 0.31 ± 0.05, 0.5 ± 0.04, 0.77 ± 0.05, 0.35 ± 0.08, 0.18 ± 0.04, P < 0.05). Furthermore, IL-1β, IL-6 and TNF-α levels in the macaques ileum and plasma were significantly higher than in the control group (plasma: 86.3 ± 15.2, 1129 ± 248.3, 77.8 ± 16.2 vs 29.5 ± 7.3, 19.8 ± 8.2, 5.6 ± 1.7; ileum: 273.4. ± 44.7, 1636 ± 168.0, 205.5 ± 30.7 vs 76.8 ± 20.5, 663.4 ± 186.9, 49.0 ± 9.4; P < 0.05).

CONCLUSION: After IIR, general inflammatory injury in the intestinal mucosa is correlated with a strong innate immune response, mediated by activation of the TLR-NF-κB-cytokine pathway.

Keywords: Intestine ischemia reperfusion, Toll-like receptors, Nuclear factor-κB, Cytokine, Macaques

Core tip: After intestine ischemia-reperfusion, general inflammatory injury of the intestinal tract, and the ensuing multiple organ dysfunction syndrome, are correlated with a strong innate immune response, which is mediated by the extensive activation of the Toll-like receptor-nuclear factor-κB-cytokine pathway throughout the whole system.