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

Mazzon E, Cuzzocrea S. Role of TNFin 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)in the defects of the TJ function. In the present study, we used tumor necrosis factor-R1 knockout mice (TNF-R1KO) to understand the roles of TNFon ileum altered permeability function in models of immobilization stress. The genetic TNFinhibition significantly reduced the degree of 1) TNFproduction in ileum tissues; 2) the alteration of zonula occludens-1 (ZO-1), claudin-2, claudin-4, claudin-5, and -catenin (immunohistochemistry); and 3) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNFreduces the tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of TNFon ileum barrier dysfunction.