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

Abstract

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