Histone Deacetylase-1 Is Enriched at the Platelet-derived Growth Factor-D Promoter in Response to Interleukin-1 beta and Forms a Cytokine-inducible Gene-silencing Complex with NF-kappa B p65 and Interferon Regulatory Factor-1 (Retracted Article. See vol 285, pg 21902, 2010)

作者：Liu Mary Y; Khachigian Levon M^*

来源：Journal of Biological Chemistry, 2009, 284(50): 35101-35112.

DOI：10.1074/jbc.M109.061903

Understanding the mechanisms governing cytokine control of growth factor expression in smooth muscle cells would provide invaluable insight into the molecular regulation of vascular phenotypes and create future opportunities for therapeutic intervention. Here, we report that the proinflammatory cytokine interleukin (IL)-1 beta suppresses platelet-derived growth factor (PDGF)-D promoter activity and mRNA and protein expression in smooth muscle cells. NF-kappa B p65, induced by IL-1 beta, interacts with a novel element in the PDGF-D promoter and inhibits PDGF-D transcription. Interferon regulatory factor-1 (IRF-1) is also induced by IL-1 beta and binds to a different element upstream in the promoter. Immunoprecipitation and chromatin immunoprecipitation experiments showed that IL-1 beta stimulates p65 interaction with IRF-1 and the accumulation of both factors at the PDGF-D promoter. Mutation of the IRF-1 and p65 DNA-binding elements relieved the promoter from IL-1 beta-mediated repression. PDGF-D repression by IL-1 beta involves histone deacetylation and interaction of HDAC-1 with IRF-1 and p65. HDAC-1 small interfering RNA ablates complex formation with IRF-1 and p65 and abrogates IRF-1 and p65 occupancy of the PDGF-D promoter. Thus, HDAC- 1 is enriched at the PDGF-D promoter in cells exposed to IL-1 beta and forms a cytokine-inducible gene-silencing complex with p65 and IRF-1.

• 出版日期2009-12-11