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The role of the peroxisome proliferator‐activated receptor‐α (PPAR‐α) in the regulation of acute inflammation
Author(s) -
Cuzzocrea Salvatore,
Mazzon Emanuela,
Di Paola Rosanna,
Peli Angelo,
Bonato Andrea,
Britti Domenico,
Genovese Tiziana,
Muià Carmelo,
Crisafulli Concetta,
Caputi Achille P.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0605341
Subject(s) - inflammation , peroxisome proliferator activated receptor , receptor , nuclear receptor , carrageenan , pleurisy , biology , tumor necrosis factor alpha , endocrinology , medicine , transcription factor , immunology , pharmacology , pleural effusion , biochemistry , gene
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.