HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print February 24, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0605341v1 79/5/999    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cuzzocrea, S. Articles by Caputi, A. P. Search for Related Content PubMed PubMed Citation Articles by Cuzzocrea, S. Articles by Caputi, A. P.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0605341

Received for publication June 24, 2005.
Revised January 7, 2006.
Accepted for publication January 12, 2006.

Article

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

Salvatore Cuzzocrea ^*@, Emanuela Mazzon ^*, Rosanna Di Paola ^*, Angelo Peli , Andrea Bonato , Domenico Britti , Tiziana Genovese ^*, Carmelo Mui ^à*, 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

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

	Abstract

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-1 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

This article has been cited by other articles:

				E. Pace, M. Ferraro, C. H. Mody, M. R. Melis, V. Scafidi, A. Bonanno, M. Profita, A. Giarratano, and M. Gjomarkaj Pleural Mesothelial Cells Express Both BLT2 and PPAR{alpha} and Mount an Integrated Response to Pleural Leukotriene B4 J. Immunol., November 15, 2008; 181(10): 7292 - 7299. [Abstract] [Full Text] [PDF]

				M. B. Schaefer, A. Pose, J. Ott, M. Hecker, A. Behnk, R. Schulz, N. Weissmann, A. Gunther, W. Seeger, and K. Mayer Peroxisome proliferator-activated receptor-{alpha} reduces inflammation and vascular leakage in a murine model of acute lung injury Eur. Respir. J., November 1, 2008; 32(5): 1344 - 1353. [Abstract] [Full Text] [PDF]

				M. B. Rosen, B. D. Abbott, D. C. Wolf, J. C. Corton, C. R. Wood, J. E. Schmid, K. P. Das, R. D. Zehr, E. T. Blair, and C. Lau Gene Profiling in the Livers of Wild-type and PPAR{alpha}-Null Mice Exposed to Perfluorooctanoic Acid Toxicol Pathol, June 1, 2008; 36(4): 592 - 607. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, S. Bruscoli, E. Mazzon, C. Crisafulli, V. Donato, R. Di Paola, E. Velardi, E. Esposito, G. Nocentini, and C. Riccardi Peroxisome Proliferator-Activated Receptor-{alpha} Contributes to the Anti-Inflammatory Activity of Glucocorticoids Mol. Pharmacol., February 1, 2008; 73(2): 323 - 337. [Abstract] [Full Text] [PDF]