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.
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References
Libby P. Inflammation in atherosclerosis. Nature, 2002, 420: 868–874
Libby P, Ridker P M, Hansson G K. Progress and challenges in translating the biology of atherosclerosis. Nature, 2011, 473: 317–325
Collins R G, Velji R, Guevara N V, et al. P-selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med, 2000, 191: 189–194
Poston R N, Haskard D O, Coucher J R, et al. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol, 1992, 140: 665–673
Myers C L, Desai S N, Schembri-King J, et al. Discriminatory effects of protein kinase inhibitors and calcium ionophore on endothelial ICAM-1 induction. Am J Physiol, 1992, 262: C365–373
Kim I, Moon S O, Kim S H, et al. Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells. J Biol Chem, 2001, 276: 7614–7620
Xue J, Thippegowda P B, Hu G, et al. NF-kappaB regulates thrombin-induced ICAM-1 gene expression in cooperation with NFAT by binding to the intronic NF-kappaB site in the ICAM-1 gene. Physiol Genomics, 2009, 38: 42–53
Blander G, Guarente L. The Sir2 family of protein deacetylases. Annu Rev Biochem, 2004, 73: 417–435
Cho K W, Lumeng C N. SirT1: a guardian at the gates of adipose tissue inflammation. Diabetes, 2011, 60: 3100–3102
Yoshizaki T, Schenk S, Imamura T, et al. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am J Physiol Endocrinol Metab, 2010, 298: E419–428
Planavila A, Iglesias R, Giralt M, et al. Sirt1 acts in association with PPARalpha to protect the heart from hypertrophy, metabolic dysregulation, and inflammation. Cardiovasc Res, 2011, 90: 276–284
Yeung F, Hoberg J E, Ramsey C S, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J, 2004, 23: 2369–2380
Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell, 2006, 127: 1109–1122
Li X, Zhang S, Blander G, et al. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell, 2007, 28: 91–106
Zhang R, Chen H Z, Liu J J, et al. SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase-2 expression in macrophages. J Biol Chem, 2010, 285: 7097–7110
Zhang Q J, Wang Z, Chen H Z, et al. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res, 2008, 80: 191–199
Stein S, Schafer N, Breitenstein A, et al. SIRT1 reduces endothelial activation without affecting vascular function in ApoE−/− mice. Aging (Albany NY), 2010, 2: 353–360
Takata T, Ishikawa F. Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression. Biochem Biophys Res Commun, 2003, 301: 250–257
Zhou S, Chen H Z, Wan Y Z, et al. Repression of P66Shc expression by SIRT1 contributes to the prevention of hyperglycemia-induced endothelial dysfunction. Circ Res, 2011, 109: 639–648
Voraberger G, Schafer R, Stratowa C. Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5′-regulatory region. Induction by cytokines and phorbol ester. J Immunol, 1991, 147: 2777–2786
Ledebur H C, Parks T P. Transcriptional regulation of the intercellular adhesion molecule-1 gene by inflammatory cytokines in human endothelial cells. Essential roles of a variant NF-kappa B site and p65 homodimers. J Biol Chem, 1995, 270: 933–943
Potente M, Dimmeler S. Emerging roles of SIRT1 in vascular endothelial homeostasis. Cell Cycle, 2008, 7: 2117–2122
Zhang H N, Li L, Gao P, Chen H Z, et al. Involvement of the p65/RelA subunit of NF-kappaB in TNF-alpha-induced SIRT1 expression in vascular smooth muscle cells. Biochem Biophys Res Commun, 2010, 397: 569–575
Yang C M, Luo S F, Hsieh H L, et al. Interleukin-1beta induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: involvement of ERK, JNK, AP-1, and NF-kappaB. J Cell Physiol, 2010, 224: 516–526
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Jia, Y., Gao, P., Chen, H. et al. SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells. Sci. China Life Sci. 56, 19–25 (2013). https://doi.org/10.1007/s11427-012-4407-7
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DOI: https://doi.org/10.1007/s11427-012-4407-7