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

Research output: Contribution to journalArticle

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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
StatePublished - Feb 1 2009

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MicroRNAs
3' Untranslated Regions
Transfection
Proteins
B7 Antigens
Messenger RNA
Jurkat Cells
Antisense Oligonucleotides
Gene Silencing
Cell Death
Epithelial Cells
Cytokines
Liver

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.

MicroRNA-513 regulates B7-H1 translation and is involved in IFN-γ-induced B7-H1 expression in cholangiocytes. / Gong, Ai Yu; Zhou, Rui; Hu, Guoku; Li, Xiaoqing; Splinter, Patrick L.; O'Hara, Steven P.; LaRusso, Nicholas F.; Soukup, Garrett; Dong, Haidong; Chen, Xian-Ming.

In: Journal of Immunology, Vol. 182, No. 3, 01.02.2009, p. 1325-1333.

Research output: Contribution to journalArticle

Gong, AY, Zhou, R, Hu, G, Li, X, Splinter, PL, O'Hara, SP, LaRusso, NF, Soukup, G, Dong, H & 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, vol. 182, no. 3, pp. 1325-1333.
Gong AY, Zhou R, Hu G, Li X, Splinter PL, O'Hara SP et al. MicroRNA-513 regulates B7-H1 translation and is involved in IFN-γ-induced B7-H1 expression in cholangiocytes. Journal of Immunology. 2009 Feb 1;182(3):1325-1333.
Gong, Ai Yu ; Zhou, Rui ; Hu, Guoku ; Li, Xiaoqing ; Splinter, Patrick L. ; O'Hara, Steven P. ; LaRusso, Nicholas F. ; Soukup, Garrett ; Dong, Haidong ; Chen, Xian-Ming. / MicroRNA-513 regulates B7-H1 translation and is involved in IFN-γ-induced B7-H1 expression in cholangiocytes. In: Journal of Immunology. 2009 ; Vol. 182, No. 3. pp. 1325-1333.
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AU - Splinter, Patrick L.

AU - O'Hara, Steven P.

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