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 Soukup, Haidong Dong, Xian-Ming Chen

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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
Pages (from-to)1325-1333
Number of pages9
JournalJournal of Immunology
Volume182
Issue number3
Publication statusPublished - Feb 1 2009

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All Science Journal Classification (ASJC) codes

  • Immunology
  • Medicine(all)

Cite this

Gong, A. Y., Zhou, R., Hu, G., Li, X., Splinter, P. L., O'Hara, S. P., ... Chen, X-M. (2009). MicroRNA-513 regulates B7-H1 translation and is involved in IFN-γ-induced B7-H1 expression in cholangiocytes. Journal of Immunology, 182(3), 1325-1333.