title: Upregulation of Toll-like receptor 2 gene expression by acetylation of AP-2 alpha in THP-1 cells, a human monocytic cell line.
abstract: Human Toll-like receptor 2 (TLR2) is a receptor for a variety of microbial products and mediates activation signals in cells of the innate immune system. Therefore, it is of great interest to investigate the molecular mechanisms that control the expression of TLR2. In this study, using real-time PCR and western blot assays, we show that trichostatin A (TSA), which is a histone deacetylase inhibitor, upregulates the expression of both TLR2 mRNA and protein in the human THP-1 cell line. A luciferase activity analysis of the truncated TLR2 promoter indicated that the region from -230 to -140 in the TLR2 promoter was sensitive to TSA. Moreover, using electrophoresis mobility shift and chromatin immunoprecipitation assays, we identified an AP-2 alpha (AP-2α) responsive element at position -184 and found that the binding of AP-2α to this element was enhanced by TSA under in vitro and in vivo conditions. Immunoprecipitation and western blot analyses showed that the levels of acetylated AP-2α were increased in THP-1 cells after TSA treatment, and this increase is consistent with the increased binding affinity to the AP-2α responsive elements. In summary, these data define a mechanism through which AP-2α acetylation and increased promoter access induce the expression of the TLR2 gene. This mechanism may provide insight into a regulatory mode of TLR2 expression and the molecular foundations of certain immunological diseases.
authors.affiliation: Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Enjie
authors.initials: E
authors.lastname: Luo
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001483:Base Sequence; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016296:Mutagenesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D006877:Hydroxamic Acids; D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D050656:Transcription Factor AP-2; C012589:trichostatin A
keywords: AP-2a; Acetylation; Gene expression; TLR2; TSA