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

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 PPARreceptor 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 PPARwild-type mice, PPARknockout mice (PPARKO) 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 PPARgene in PPARKO 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 PPARgene 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 PPARmice strongly suggests that a PPARpathway modulates the degree of acute inflammation in the mice. J. Leukoc. Biol. 79: 000–000; 2006.