NS-398, a selective COX-2 inhibitor, inhibits proliferation of IL-1{beta}-stimulated vascular smooth muscle cells by induction of {eta}{omicron}-1
- Department of Pharmacology and Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)
- Department of Microbiology and Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)
We investigated whether NS-398, a selective inhibitor of COX-2, induces HO-1 in IL-1{beta}-stimulated vascular smooth muscle cells (VSMC). NS-398 reduced the production of PGE{sub 2} without modulation of expression of COX-2 in IL-1{beta}-stimulated VSMC. NS-398 increased HO-1 mRNA and protein in a dose-dependent manner, but inhibited proliferation of IL-1{beta}-stimulated VSMC. Furthermore, SnPPIX, a HO-1 inhibitor, reversed the effects of NS-398 on PGE{sub 2} production, suggesting that COX-2 activity can be affected by HO-1. Hemin, a HO-1 inducer, also reduced the production of PGE{sub 2} and proliferation of IL-1{beta}-stimulated VSMC. CORM-2, a CO-releasing molecule, but not bilirubin inhibited proliferation of IL-1{beta}-stimulated VSMC. NS-398 inhibited proliferation of IL-1{beta}-stimulated VSMC in a HbO{sub 2}-sensitive manner. In conclusion, NS-398 inhibits proliferation of IL-1{beta}-stimulated VSMC by HO-1-derived CO. Thus, NS-398 may facilitate the healing process of vessels in vascular inflammatory disorders such as atherosclerosis.
- OSTI ID:
- 21217116
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 376, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2008.09.056; PII: S0006-291X(08)01828-7; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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