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

被引：21

作者：

Choi, Hyoung Chul ^{[3
,4
]}

Kim, Hee Sun ^{[3
,5
]}

Lee, Kwang Youn ^{[3
,4
]}

Chang, Ki Churl ^{[1
,2
]}

Kang, Young Jin ^{[3
,4
]}

机构：

[1] Gyeongsang Natl Univ, Dept Pharmacol, Sch Med, Jinju 660751, South Korea

[2] Gyeongsang Natl Univ, Inst Hlth Sci, Jinju 660751, South Korea

[3] Yeungnam Univ, Coll Med, Aging Associated Vasc Dis Res Ctr, Taegu 705717, South Korea

[4] Yeungnam Univ, Dept Pharmacol, Taegu 705717, South Korea

[5] Yeungnam Univ, Dept Microbiol, Taegu 705717, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 376卷 / 04期

关键词：

Heme oxygenase-1; Vascular smooth muscle cell; Proliferation; Inflammation; Atherosclerosis;

D O I：

10.1016/j.bbrc.2008.09.056

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(2) without modulation of expression of COX-2 in IL-1 beta-stimulated VSMC. NS-398 increased HO-I mRNA and protein in a dose-dependent manner, but inhibited proliferation of IL-beta-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-beta-stimulated VSMC. CORM-2, a CO-releasing molecule, but not bilirubin inhibited proliferation of IL-beta-stimulated VSMC. NS-398 inhibited proliferation of IL-beta-stimulated VSMC in a HbO(2)-sensitive manner. In conclusion, NS-398 inhibits proliferation of IL-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. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：753 / 757

页数：5

共 23 条

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