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SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

查看全文 作　　者：JIA [1]YuYan;GAO [1]Peng;CHEN [1]HouZao;WAN [1]YanZhen;ZHANG [1]Ran;ZHANG [1]ZhuQin;YANG [1]RuiFeng;WANG [1]Xu;XU [1]Jing;LIU [1]DePei 高影响力作者 机构地区：[1]State Key Laboratory of Medical Molecular Biology,Department of Biochemistry and Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College高影响力机构 出　　处：《Science China(Life Sciences)》索引2013年第56卷第1期,共7页高影响力期刊 基　　金：supported by National Natural Science Foundation of China(31271227,31028005,31021091);National Basic Research Program of China (2011CB503902,2012BAI39B03) 摘　　要：Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin (PMA/Io) in human umbilical vein endothelial cells (HUVECs). Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression in HUVECs. Knockdown of SIRT1 by RNA interference (RNAi) resulted in increased expression of ICAM-1 in HUVECs. Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation (ChIP) assays. Furthermore, SIRT1 RNAi increased NF-κB p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect. 关 键 词：ICAM-1 血管内皮细胞 诱导条件 离子霉素 PMA 人脐静脉内皮细胞 细胞间粘附分子-1 动脉粥样硬化
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