Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0605341 on February 24, 2006

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-{alpha} (PPAR-{alpha}) in the regulation of acute inflammation

Salvatore Cuzzocrea*,§,1, Emanuela Mazzon*,§, Rosanna Di Paola*, Angelo Peli{dagger}, Andrea Bonato{dagger}, Domenico Britti{ddagger}, 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;
{dagger} Clinical Veterinary Department Alma Mater Studiorum, University of Bologna, Italy; and
{ddagger} 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-{alpha} (PPAR-{alpha}) 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-{alpha} 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-{alpha} wild-type mice, PPAR-{alpha} knockout mice (PPAR-{alpha}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-{alpha} gene in PPAR-{alpha}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-{alpha} gene enhanced the staining (immunohistochemistry) for FAS ligand in the paw and in the lung and the expression of tumor necrosis factor {alpha} and interleukin-1ß in the lungs of carrageenan-treated mice. In conclusion, the increased inflammatory response observed in PPAR-{alpha}KO mice strongly suggests that a PPAR-{alpha} 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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