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Alterations in the gut barrier and involvement of Toll‐like receptor 4 in murine postoperative ileus
Author(s) -
Lin S.S.,
Zhang R.Q.,
Shen L.,
Xu X.J.,
Li K.,
Bazhin A.V.,
Fichna J.,
Li Y.Y.
Publication year - 2018
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13286
Subject(s) - tlr4 , inflammation , toll like receptor , knockout mouse , receptor , lipopolysaccharide binding protein , lipopolysaccharide , biology , immunology , endocrinology , medicine , innate immune system , acute phase protein
Abstract Background The changes in the gut barrier ( GB ) and associated mechanisms in postoperative ileus ( POI ) are still unclear. Toll‐like receptor 4 ( TLR 4) is involved in inflammation, which may cause GB dysfunction and POI . Here, the roles of the GB in POI in relation to TLR 4‐dependent signaling pathways were explored. Methods POI was induced by small bowel manipulation in wild‐type ( WT ) and TLR 4‐knockout ( TLR 4−/− ) mice. Twenty‐four hours after manipulation, indices of gastrointestinal ( GI ) transit, GB structure and function, inflammation, and related signaling pathways were analyzed. Key Results Normal GI motility and GB function were not affected by TLR 4 knockout. Compared with WT POI mice, TLR 4−/− POI mice showed milder GI transit retardation, GB dysfunction, and inflammatory responses. In WT mice, GB disorder was characterized by colonic goblet cells depletion, increased gut claudin‐2 expression, and decreased CD 4+/ CD 8+ ratios in intestinal Peyer's patches. Green fluorescent protein‐tagged Escherichia coli in the gut was detected in plasma and extraintestinal organs, followed with increased plasma lipopolysaccharide. These changes displayed in WT POI mice were less severe in TLR 4−/− POI mice. Furthermore, the mRNA and protein expression of interleukin‐6, monocyte chemotactic protein‐1, pp38 and pJNK in the intestine, and TNF ‐α level in plasma were significantly increased in WT , but not TLR 4−/− POI mice. Conclusions & Inferences These results indicate that GB is impaired in the experimental POI , with inflammation being involved in this pathological process. TLR 4 deficiency alleviated GB dysfunction and suppressed inflammation by disrupting the activation of mitogen‐activated protein kinase signaling pathways, thereby ameliorating POI .