Troglitazone increases IL-1β induced cyclooxygenase-2 and inducible nitric oxide synthase expression via enhanced phosphorylation of IκBα in vascular smooth muscle cells from Wistar-Kyoto rats and spontaneously hypertensive rats

Peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 PPAR gamma agonists of thiazolidinediones. We report here that troglitazone but not ciglitazone increased IL-1 beta 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 kappa B (I kappa B) activation. Troglitazone treatment of these cells also resulted in a dosedependent increase in IL-1 beta induced I kappa B alpha phosphorylation. These data suggest that troglitazone is capable of increasing IL-1 beta induced COX-2 and NOS expression through an I kappa B alpha dependent mechanism in VSMC from WKY and SHR.