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

Role of TNF-alpha in ileum tight junction alteration in mouse model of restraint stress. Am J Physiol Gastrointest Liver Physiol 294: G1268-G1280, 2008. First published February 28, 2008; doi:10.1152/ajpgi.00014.2008.-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.