title: SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells.
abstract: 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.
authors.affiliation: 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, Beijing, 100005, People's Republic of China.
authors.forename: YuYan
authors.initials: Y
authors.lastname: Jia
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: HouZao
authors.initials: H
authors.lastname: Chen
authors.forename: YanZhen
authors.initials: Y
authors.lastname: Wan
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: ZhuQin
authors.initials: Z
authors.lastname: Zhang
authors.forename: RuiFeng
authors.initials: R
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: DePei
authors.initials: D
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression / Q000235:genetics; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D015759:Ionomycin; D008156:Luciferases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D013755:Tetradecanoylphorbol Acetate