Role of TNF-α in muscularis inflammation and motility disorder in a TNBS-induced colitis model: clues from TNF-α-deficient mice

Authors: kinoshita, k.¹; hori, m.¹; fujisawa, m.¹; sato, k.¹; ohama, t.¹; momotani, e.²; ozaki, h.¹

Source: Neurogastroenterology and Motility, Volume 18, Number 7, July 2006 , pp. 578-588(11)

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Abstract:

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-α (TNF-α)^−/− 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-α^−/− mouse colon. After the induction of inflammation with TNBS, the levels of proinflammatory cytokines, such as TNF-α, interleukin-1β 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-α^−/− 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-α^−/− mice. Finally, using the organ culture method, we found that TNF-α directly (independent of mucosal inflammation) disturbs the smooth muscle function. These results suggest that TNF-α 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-α directly induces motor dysfunctions by acting on the smooth muscle.

Keywords: gut inflammation; intestinal motility; smooth muscle; tumour necrosis factor-α

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2982.2006.00784.x

Affiliations: 1: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan 2: National Institute of Animal Health, Tsukuba, Ibaraki, Japan

Publication date: 2006-07-01

Role of TNF-α in muscularis inflammation and motility disorder in a TNBS-induced colitis model: clues from TNF-α-deficient mice

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