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

AY Gong, R Zhou, G Hu, X Li, PL Splinter… - The Journal of …, 2009 - journals.aai.org
AY Gong, R Zhou, G Hu, X Li, PL Splinter, SP O'Hara, NF LaRusso, GA Soukup, H Dong
The Journal of Immunology, 2009journals.aai.org
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-γ induces B7-H1 protein expression and alters the microRNA (miRNA) expression …
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-γ induces 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.
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