MicroRNA-513 regulates B7-H1 translation and is involved in IFN-γ-induced B7-H1 expression in cholangiocytes

Ai Yu Gong, Rui Zhou, Guoku Hu, Xiaoqing Li, Patrick L. Splinter, Steven P. O'Hara, Nicholas F. LaRusso, Garrett A. Soukup, Haidong Dong, Xian Ming Chen

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Biliary epithelial cells (cholangiocytes) respond to proinflammatory cytokines such as IFN-γ 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-γinduces B7-H1 protein expression and alters the microRNA (miRNA) expression profile in cholangiocytes. Of those IFN-γ-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-γ-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-γ-induced B7-H1 expression in human cholangiocytes, suggesting a role for miRNA-mediated gene silencing in the regulation of cholangiocyte response to IFN-γ.

Original languageEnglish (US)
Pages (from-to)1325-1333
Number of pages9
JournalJournal of Immunology
Volume182
Issue number3
DOIs
StatePublished - Feb 1 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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