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

Journal of Leukocyte Biology

Emanuela Mazzon¹  Tiziana Genovese³  Carmelo Muià³  Angelo Peli²  Andrea Bonato²  Domenico Britti⁴  Achille P. Caputi³  Salvatore Cuzzocrea¹  Concetta Crisafulli³  Rosanna Di Paola³ 

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

关键词: carrageenan-induced paw edema;    carrageenan-induced pleurisy;    cytokines;    neutrophil infiltration;   

DOI  :  10.1189/jlb.0605341

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The peroxisome proliferator-activated receptor-α (PPAR-α) 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-α 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-α wild-type mice, PPAR-α knockout mice (PPAR-αKO) 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-α gene in PPAR-αKO 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-α gene enhanced the staining (immunohistochemistry) for FAS ligand in the paw and in the lung and the expression of tumor necrosis factor α and interleukin-1β in the lungs of carrageenan-treated mice. In conclusion, the increased inflammatory response observed in PPAR-αΚΟ mice strongly suggests that a PPAR-α pathway modulates the degree of acute inflammation in the mice.

【 授权许可】

Unknown