title: The role of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in the regulation of acute inflammation.
abstract: 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-alphaKO) 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-alphaKO 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-1beta in the lungs of carrageenan-treated mice. In conclusion, the increased inflammatory response observed in PPAR-alphaKO mice strongly suggests that a PPAR-alpha pathway modulates the degree of acute inflammation in the mice.
authors.affiliation: Dipartment Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina Torre Biologica, Policlinico Universitario, Italy. salvator@unime.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Angelo
authors.initials: A
authors.lastname: Peli
authors.forename: Andrea
authors.initials: A
authors.lastname: Bonato
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Carmelo
authors.initials: C
authors.lastname: Muià
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
mesh_terms: D000208:Acute Disease; D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D053222:Fas Ligand Protein; D005260:Female; D005528:Foot / Q000503:physiopathology; D007155:Immunologic Factors / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007155:Immunologic Factors; D018836:Inflammation Mediators; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D002351:Carrageenan