Role of TNF-alpha in ileum tight junction alteration in mouse model of restraint stress.

Restraint stress induces permeability changes in the small intestine, but little is known about the role of tumor necrosis factor (TNF)-alpha in the defects of the TJ function. In the present study, we used tumor necrosis factor-R1 knockout mice (TNF-alpha-R1KO) to understand the roles of TNF-alpha on ileum altered permeability function in models of immobilization stress. The genetic TNF-alpha inhibition significantly reduced the degree of 1) TNF-alpha production in ileum tissues; 2) the alteration of zonula occludens-1 (ZO-1), claudin-2, claudin-4, claudin-5, and beta-catenin (immunohistochemistry); and 3) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-alpha reduces the tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of TNF-alpha on ileum barrier dysfunction.