Cerivastatin suppresses lipopolysaccharide-induced ICAM-1 expression through inhibition of Rho GTPase in BAEC

被引:109
作者
Takeuchi, S [1 ]
Kawashima, S [1 ]
Rikitake, Y [1 ]
Ueyama, T [1 ]
Inoue, N [1 ]
Hirata, K [1 ]
Yokoyama, M [1 ]
机构
[1] Kobe Univ, Sch Med, Dept Internal Med 1, Chuo Ku, Kobe, Hyogo 6500017, Japan
关键词
D O I
10.1006/bbrc.2000.2238
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 the effect of cerivastatin on lipopolysaccharide (LPS)-induced intercellular adhesion molecule-1 (ICAM-1) expression in bovine aortic endothelial cells. Cerivastatin suppressed LPS-induced ICAM-1 mRNA expression. Cotreatment with geranylgeranylpyrophosphate reversed the effect of cerivastatin. Because Rho undergoes geranylgeranyl modification, we elucidated whether Rho is involved in LPS-induced ICAM-1 expression. Inhibition of Rho activity by Clostridium botulinum C3 transferase or by overexpression of RhoA T19N, a dominant-negative mutant of RhoA, decreased LPS-induced ICAM-1 expression. Although cerivastatin up-regulated endothelial nitric oxide synthase (eNOS), inhibition of nitric oxide (NO) synthesis by cotreatment with N-omega-nitro-L-arginine methyl ester (L-NAME) exhibited no influence on the effect of cerivastatin. The present results indicate that cerivastatin prevents LPS-induced ICAM-1 expression in endothelial cells via inhibition of Rho activity. This inhibitory effect is likely unrelated to up-regulation of eNOS. (C) 2000 Academic Press.
引用
收藏
页码:97 / 102
页数:6
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