Role of TNF‐<i>α</i> in muscularis inflammation and motility disorder in a TNBS‐induced colitis model: clues from TNF‐<i>α</i>‐deficient mice

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<jats:p><jats:bold>Abstract </jats:bold> Macroscopic and histological analysis revealed that the colonic inflammation induced by 2,4,6‐trinitrobenzenesulphonic acid (TNBS) was of lower grade in tumour necrosis factor‐<jats:italic>α</jats:italic> (TNF‐<jats:italic>α</jats:italic>)<jats:sup>−/−</jats:sup> mice than in wild‐type mice. Myeloperoxidase activity, an indicator of neutrophilic infiltration, was also low in both the mucosal and smooth muscle layer of the TNF‐<jats:italic>α</jats:italic><jats:sup>−/−</jats:sup> mouse colon. After the induction of inflammation with TNBS, the levels of proinflammatory cytokines, such as TNF‐<jats:italic>α</jats:italic>, interleukin‐1<jats:italic>β</jats:italic> and interleukin‐6, were elevated both in the inflamed mucosa and muscle layers in the wild‐type mice; however, the productions of these cytokines were greatly reduced in the TNF‐<jats:italic>α</jats:italic><jats:sup>−/−</jats:sup> mouse colon. The contractions of isolated colonic smooth muscle strips induced by several stimulatory agents were significantly decreased after treatment with TNBS in wild‐type mice; however, these contractions were scarcely affected in TNF‐<jats:italic>α</jats:italic><jats:sup>−/−</jats:sup> mice. Finally, using the organ culture method, we found that TNF‐<jats:italic>α</jats:italic> directly (independent of mucosal inflammation) disturbs the smooth muscle function. These results suggest that TNF‐<jats:italic>α</jats:italic> plays an essential role not only in mucosal inflammation but also in muscularis inflammation in the colon of mice with TNBS‐induced colitis, and that TNF‐<jats:italic>α</jats:italic> directly induces motor dysfunctions by acting on the smooth muscle.</jats:p>

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