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

• Published in: Biological and Pharmaceutical Bulletin Vol. 31; no. 10; pp. 1955 - 1958
• Main Authors: Kang, Young Jin, Kim, Hee Sun, Choi, Hyoung Chul
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 01.10.2008
• Subjects: cyclooxygenase-2; inducible nitric oxide synthase; spontaneously hypertensive rat; troglitazone; Wistar-Kyoto rat
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.1955

Peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ agonists of thiazolidinediones. We report here that troglitazone but not ciglitazone increased IL-1β 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 κB (IκB) activation. Troglitazone treatment of these cells also resulted in a dose-dependent increase in IL-1β induced IκBα phosphorylation. These data suggest that troglitazone is capable of increasing IL-1β induced COX-2 and iNOS expression through an IκBα dependent mechanism in VSMC from WKY and SHR.