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Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the thiazolidinedione class are widely used for the treatment of type 2 diabetes subjects due to their ability to improve insulin resistance. Troglitazone and ciglitazone belong to the PPARgamma agonists of thiazolidinediones. We report here that troglitazone but not ciglitazone increased IL-1beta induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in vascular smooth muscle cell (VSMC) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Potentiated expression of COX-2 and iNOS by troglitazone was inhibited by MG-132, a specific inhibitor of inhibitory factor kappaB (IkappaB) activation. Troglitazone treatment of these cells also resulted in a dose-dependent increase in IL-1beta induced IkappaBalpha phosphorylation. These data suggest that troglitazone is capable of increasing IL-1beta induced COX-2 and iNOS expression through an IkappaBalpha dependent mechanism in VSMC from WKY and SHR.

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Troglitazone Increases IL-1.BETA. Induced Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression via Enhanced Phosphorylation of I.KAPPA.B.ALPHA. in Vascular Smooth Muscle Cells from Wistar-Kyoto Rats and Spontaneously Hypertensive Rats