Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 79, Issue 5, Pages 999-1010Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0605341
Keywords
carrageenan-induced paw edema; carrageenan-induced pleurisy; cytokines; neutrophil infiltration
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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-alpha KO) 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-KO juice 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-1 beta in the lungs of carrageenan-treated mice. In conclusion, the increased inflammatory response observed in PPAR-alpha KO mice strongly suggests that a PPAR-alpha pathway modulates the degree of acute inflammation in the mice.
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