Intestinal ischemia-reperfusion of macaques triggers a strong innate immune response.
OBJECTIVE
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).


CONCLUSIONS
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.
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.
Hao
H
Wu
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
YY
Deng
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.
Ling
L
Liu
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.
Qing-Hua
QH
Tan
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.
Chun-Hui
CH
Wang
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.
Mei-Mei
MM
Guo
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.
Yong-Mei
YM
Xie
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.
Cheng-Wei
CW
Tang
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000276:immunology* / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D065666:Mesenteric Ischemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009102:Multiple Organ Failure / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D051193:Toll-Like Receptors
Cytokine; Intestine ischemia reperfusion; Macaques; Nuclear factor-κB; Toll-like receptors