Role Of Pioglitazone, An Agonist Of The Peroxisome Proliferator-Activated Receptor Gamma, In Resolution Of Gouty Inflammations

Abstract Objective To investigate the role of pioglitazone, an Agonist of PPARy, in resolution of MSU crystal-induced inflammations. Methods Animal arthritis and peritonitis, as well as air-pouch inflammation models were induced by MSU crystals. Effects of pioglitazone were evaluated in these models. Expressions of PPARy, TNF-α, IL-1β, IL-1Ra, IFNγ, IL-4, CINC, S100A8 and S100A9 were determined by RT-PCR. Results Pioglitazone significantly reduced the severities of arthritis, peritonitis and air-pouch inflammations associated with gout. PPARy was predominantly expressed in macrophage, and its expressions were correlated negatively with the severities of peritonitis. Expressions of TNF-a, CINC, S100A8, S100A9 and IFNy in synovium were suppressed, while that of IL-4 was augmented, and S100A8/S100A9 expressions in activated peritoneal macrophages were down regulated by pioglitazone as well. Conclusion PPARy may participate in MSU induced inflammations. The results indicated the anti-inflammatory properties of pioglitazone on these gouty models with mechanisms involving promotion of macrophage differentiation and maturation, as well as regulation of some key cytokines. It is suggested that PPARy play an important role in gouty inflammations.