TY - JOUR
T1 - MicroRNA-513 regulates B7-H1 translation and is involved in IFN-γ-induced B7-H1 expression in cholangiocytes
AU - Gong, Ai Yu
AU - Zhou, Rui
AU - Hu, Guoku
AU - Li, Xiaoqing
AU - Splinter, Patrick L.
AU - O'Hara, Steven P.
AU - LaRusso, Nicholas F.
AU - Soukup, Garrett A.
AU - Dong, Haidong
AU - Chen, Xian Ming
PY - 2009/2/1
Y1 - 2009/2/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.182.3.1325
DO - 10.4049/jimmunol.182.3.1325
M3 - Article
C2 - 19155478
AN - SCOPUS:63149085789
SN - 0022-1767
VL - 182
SP - 1325
EP - 1333
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -