title: MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes.
abstract: Biliary epithelial cells (cholangiocytes) respond to proinflammatory cytokines such as IFN-gamma and actively participate in the regulation of biliary inflammatory response in the liver. B7-H1 (also known as CD274 or PD-L1) is a member of the B7 costimulatory molecules and plays a critical immunoregulatory role in cell-mediated immune responses. In this study, we show that resting human cholangiocytes in culture express B7-H1 mRNA, but not B7-H1 protein. IFN-gamma induces B7-H1 protein expression and alters the microRNA (miRNA) expression profile in cholangiocytes. Of those IFN-gamma-down-regulated miRNAs, we identified microRNA-513 (miR-513) with complementarity to the 3'-untranslated region of B7-H1 mRNA. Targeting of the B7-H1 3'-untranslated region by miR-513 results in translational repression. Transfection of cholangiocytes with an antisense oligonucleotide to miR-513 induces B7-H1 protein expression. Additionally, transfection of miR-513 precursor decreases IFN-gamma-induced B7-H1 protein expression and consequently influences B7-H1-associated apoptotic cell death in cocultured Jurkat cells. Thus, miR-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in human cholangiocytes, suggesting a role for miRNA-mediated gene silencing in the regulation of cholangiocyte response to IFN-gamma.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE 68178, USA.
authors.forename: Ai-Yu
authors.initials: AY
authors.lastname: Gong
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Guoku
authors.initials: G
authors.lastname: Hu
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Splinter
authors.forename: Steven P
authors.initials: SP
authors.lastname: O'Hara
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: LaRusso
authors.forename: Garrett A
authors.initials: GA
authors.lastname: Soukup
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Chen
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D060890:B7-H1 Antigen; D001652:Bile Ducts / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D019169:Jurkat Cells; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis; D050794:STAT1 Transcription Factor / Q000502:physiology
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018836:Inflammation Mediators; D035683:MicroRNAs; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma