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Am J Physiol Gastrointest Liver Physiol 297: G488-G505, 2009. First published June 25, 2009; doi:10.1152/ajpgi.00023.2009
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INFLAMMATION/IMMUNITY/MEDIATORS

Role of peroxisome proliferator-activated receptor-{alpha} in ileum tight junction alteration in mouse model of restraint stress

Emanuela Mazzon,1 Concetta Crisafulli,2 Maria Galuppo,2 and Salvatore Cuzzocrea1,2

1Istituto di Ricovero e Cura a Carattere Scientifico Centro Neurolesi "Bonino-Pulejo," Messina; and 2Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy

Submitted 21 January 2009 ; accepted in final form 19 June 2009

Restraint stress induces permeability changes in the small intestine, but little is known about the role of endogenous peroxisome proliferator-activated receptor-{alpha} (PPAR-{alpha}) ligand in the defects of the tight junction function. In the present study, we used PPAR-{alpha} knockout mice to understand the roles of endogenous PPAR-{alpha} on ileum altered permeability function in models of immobilization stress. The absence of a functional PPAR-{alpha} gene in PPAR-{alpha} knockout mice resulted in a significant augmentation of the degree of 1) TNF-{alpha} production in ileum tissues; 2) the alteration of zonula occludens-1, occludin, and β-catenin (immunohistochemistry); and 3) apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that endogenous PPAR-{alpha} ligands reduce the degree of tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of endogenous PPAR-{alpha} ligands on ileum barrier dysfunction.

apoptosis; peroxisome proliferator-activated receptor-{alpha}-deficient mice; zonula occludens-1; occludin; β-catenin


Address for reprint requests and other correspondence: S. Cuzzocrea, Institute of Pharmacology, School of Medicine, Univ. of Messina, via C. Valeria, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy (e-mail: salvator{at}unime.it)






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