Takeuchi S, Kawashima S, Rikitake Y, Ueyama T, Inoue N, Hirata K, Yokoyama M
First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Biochem Biophys Res Commun. 2000 Mar 5;269(1):97-102. doi: 10.1006/bbrc.2000.2238.
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.
我们研究了西立伐他汀对脂多糖（LPS）诱导的牛主动脉内皮细胞细胞间黏附分子-1（ICAM-1）表达的影响。西立伐他汀抑制LPS诱导的ICAM-1 mRNA表达。与香叶基香叶基焦磷酸共同处理可逆转西立伐他汀的作用。由于Rho会发生香叶基香叶基修饰，我们阐明了Rho是否参与LPS诱导的ICAM-1表达。肉毒杆菌C3转移酶抑制Rho活性或过表达RhoA T19N（RhoA的显性负性突变体）可降低LPS诱导的ICAM-1表达。尽管西立伐他汀上调了内皮型一氧化氮合酶（eNOS），但与N（ω）-硝基-L-精氨酸甲酯（L-NAME）共同处理抑制一氧化氮（NO）合成对西立伐他汀的作用没有影响。目前的结果表明，西立伐他汀通过抑制Rho活性来预防LPS诱导的内皮细胞ICAM-1表达。这种抑制作用可能与eNOS的上调无关。
