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Biochem Biophys Res Commun. 2008 Nov 28;376(4):753-7. doi: 10.1016/j.bbrc.2008.09.056. Epub 2008 Sep 20.

NS-398, a selective COX-2 inhibitor, inhibits proliferation of IL-1beta-stimulated vascular smooth muscle cells by induction of HO-1.

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  • 1Department of Pharmacology and Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.

Abstract

We investigated whether NS-398, a selective inhibitor of COX-2, induces HO-1 in IL-1beta-stimulated vascular smooth muscle cells (VSMC). NS-398 reduced the production of PGE(2) without modulation of expression of COX-2 in IL-1beta-stimulated VSMC. NS-398 increased HO-1 mRNA and protein in a dose-dependent manner, but inhibited proliferation of IL-1beta-stimulated VSMC. Furthermore, SnPPIX, a HO-1 inhibitor, reversed the effects of NS-398 on PGE(2) production, suggesting that COX-2 activity can be affected by HO-1. Hemin, a HO-1 inducer, also reduced the production of PGE(2) and proliferation of IL-1beta-stimulated VSMC. CORM-2, a CO-releasing molecule, but not bilirubin inhibited proliferation of IL-1beta-stimulated VSMC. NS-398 inhibited proliferation of IL-1beta-stimulated VSMC in a HbO(2)-sensitive manner. In conclusion, NS-398 inhibits proliferation of IL-1beta-stimulated VSMC by HO-1-derived CO. Thus, NS-398 may facilitate the healing process of vessels in vascular inflammatory disorders such as atherosclerosis.

PMID:
18809379
[PubMed - indexed for MEDLINE]
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