Troglitazone increases IL-1beta induced cyclooxygenase-2 and inducible nitric oxide synthase expression via enhanced phosphorylation of IkappaBalpha in vascular smooth muscle cells from Wistar-Kyoto rats and spontaneously hypertensive rats.
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.
Kang
Young Jin
YJ
Department of Pharmacology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
Kim
Hee Sun
HS
Choi
Hyoung Chul
HC
D000818:Animals; D015153:Blotting, Western; D002839:Chromans / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D000077288:Troglitazone