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Am J Physiol Gastrointest Liver Physiol (February 28, 2008). doi:10.1152/ajpgi.00014.2008
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Submitted on January 9, 2008
Accepted on February 26, 2008

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

Emanuela Mazzon1 and Salvatore Cuzzocrea1*

1 university of messina, messina, Italy

* To whom correspondence should be addressed. E-mail: salvator{at}unime.it.

Restraint stress induces permeability changes in the small intestine but little is known on the role of TNF-{alpha} in the defects of the TJ function. In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-{alpha}R1KO) to understand the roles of TNF-{alpha} on ileum altered permeability function in models of immobilisation stress. The genetic TNF-{alpha} inhibition significantly reduced the degree of (1) TNF-{alpha} production in ileum tissues, (2) the alteration of 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 immobilisation stress, suggesting a possible role of TNF-{alpha} on ileum barrier dysfunction.




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