Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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The aim of the present study was to evaluate the role of endogenous and exogenous peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear receptor, on the regulation of inflammation in macrophages. To address this question, we have stimulated peritoneal macrophages from PPAR-alpha wild-type mice and PPAR-alpha knockout mice (PPAR-alpha) with 10 microg/mL LPS and 100 U/mL IFN-gamma. We report here that the absence of a functional PPAR-alpha gene in PPAR-alpha knockout mice resulted in a significant augmentation of various inflammatory parameters in peritoneal macrophages. ⋯ To elucidate whether the protective effects of clofibrate is related to activation of the PPAR-alpha receptor, we also investigated the effect of clofibrate treatment on PPAR-alpha-deficient mice. The absence of the PPAR-alpha receptor significantly abolished the protective effect of the PPAR-alpha agonist against LPS/IFN-gamma-induced macrophage inflammation. In conclusion, our study demonstrates that the endogenous and exogenous PPAR-alpha ligands reduce the degree of macrophage inflammation caused by LPS/IFN-gamma stimulation.