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

J Immunol. 2009 Feb 1;182(3):1325-33. doi: 10.4049/jimmunol.182.3.1325.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism*
  • B7-H1 Antigen
  • Bile Ducts / immunology*
  • Bile Ducts / metabolism*
  • Bile Ducts / pathology
  • Cell Line, Transformed
  • Coculture Techniques
  • Gene Expression Profiling
  • Humans
  • Inflammation Mediators / physiology
  • Interferon-gamma / physiology*
  • Jurkat Cells
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / physiology*
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / biosynthesis
  • STAT1 Transcription Factor / physiology

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • Inflammation Mediators
  • MicroRNAs
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interferon-gamma