MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes.
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.
Gong
Ai-Yu
AY
Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE 68178, USA.
Zhou
Rui
R
Hu
Guoku
G
Li
Xiaoqing
X
Splinter
Patrick L
PL
O'Hara
Steven P
SP
LaRusso
Nicholas F
NF
Soukup
Garrett A
GA
Dong
Haidong
H
Chen
Xian-Ming
XM
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D060890:B7-H1 Antigen; D001652:Bile Ducts / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D019169:Jurkat Cells; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis; D050794:STAT1 Transcription Factor / Q000502:physiology
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018836:Inflammation Mediators; D035683:MicroRNAs; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma