Published online before print February 24, 2006

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(Journal of Leukocyte Biology. 2006;79:999-1010.)
© 2006 by Society for Leukocyte Biology

The role of the peroxisome proliferator-activated receptor- (PPAR-) in the regulation of acute inflammation

Salvatore Cuzzocrea^*,,1, Emanuela Mazzon^*,, Rosanna Di Paola^*, Angelo Peli, Andrea Bonato, Domenico Britti, Tiziana Genovese^*, Carmelo Muià^*, Concetta Crisafulli^* and Achille P. Caputi^*

^* Dipartment Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina Torre Biologica, Policlinico Universitario, Italy;
Clinical Veterinary Department Alma Mater Studiorum, University of Bologna, Italy; and
Department of Veterinary Clinical Science, University of Teramo, Italy; and
Centro per lo Studio edil Trattamento dei Neurolesi Lungodegenti, Facoltà di Medicina e Chirurgia, University of Messina, Italy

¹Correspondence: Institute of Pharmacology, School of Medicine, University of Messina, via C. Valeria, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy. E-mail: salvator{at}unime.it

The peroxisome proliferator-activated receptor- (PPAR-) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study was to evaluate the role of the PPAR- receptor on the development of acute inflammation. To address this question, we used two animal models of acute inflammation (carrageenan-induced paw edema and carrageenan-induced pleurisy). We report here that when compared with PPAR- wild-type mice, PPAR- knockout mice (PPAR-KO) mice experienced a higher rate of the extent and severity when subjected to carrageenan injection in the paw edema model or to carrageenan administration in the pleurisy model. In particular, the absence of a functional PPAR- gene in PPAR-KO mice resulted in a significant augmentation of various inflammatory parameters (e.g., enhancement of paw edema, pleural exudate formation, mononuclear cell infiltration, and histological injury) in vivo. Furthermore, the absence of a functional PPAR- gene enhanced the staining (immunohistochemistry) for FAS ligand in the paw and in the lung and the expression of tumor necrosis factor and interleukin-1ß in the lungs of carrageenan-treated mice. In conclusion, the increased inflammatory response observed in PPAR-KO mice strongly suggests that a PPAR- pathway modulates the degree of acute inflammation in the mice.

Key Words: carrageenan-induced paw edema • carrageenan-induced pleurisy • cytokines • neutrophil infiltration

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