Document Detail

miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes.
MedLine Citation:
PMID:  20110463     Owner:  NLM     Status:  MEDLINE    
Aberrant cholangiocyte reactions in response to inflammatory stimuli are important pathogenic factors for the persistent biliary inflammation in patients with cholangiopathies. Overexpression of intercellular cell adhesion molecule-1 (ICAM-1) in cholangiocytes is a common pathological feature in inflammatory cholangiopathies and can promote cholangiocyte interactions with effector lymphocytes in the portal region. In this study, we tested the involvement of miRNA-mediated posttranscriptional regulation in IFN-gamma-induced ICAM-1 expression in cholangiocytes. Using both immortalized and nonimmortalized human cholangiocyte cell lines, we found that IFN-gamma activated ICAM-1 transcription and increased ICAM-1 protein expression. Inhibition of ICAM-1 transcription could only partially block IFN-gamma-induced ICAM-1 expression at the protein level. In silico target prediction analysis revealed complementarity of miR-221 to the 3'-untranslated region of ICAM-1 mRNA. Targeting of ICAM-1 3'-untranslated region by miR-221 resulted in translational repression in cholangiocytes but not ICAM-1 mRNA degradation. Functional inhibition of miR-221 with anti-miR-221 induced ICAM-1 protein expression. Moreover, IFN-gamma stimulation decreased miR-221 expression in cholangiocytes in a signal transducer and activator of transcription 1-dependent manner. Transfection of miR-221 precursor abolished IFN-gamma-stimulated ICAM-1 protein expression. In addition, miR-221-mediated expression of ICAM-1 on cholangiocytes showed a significant influence on the adherence of cocultured T cells. These findings indicate that both transcriptional and miRNA-mediated posttranscriptional mechanisms are involved in IFN-gamma-induced ICAM-1 expression in human cholangiocytes, suggesting an important role for miRNAs in the regulation of cholangiocyte inflammatory responses.
Guoku Hu; Ai-Yu Gong; Jun Liu; Rui Zhou; Caishu Deng; Xian-Ming Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-28
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  298     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-04-16     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G542-50     Citation Subset:  IM    
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MeSH Terms
3' Untranslated Regions / genetics
Bile Ducts / cytology*
Cell Adhesion / drug effects,  genetics
Cell Line, Transformed
Cell Survival / drug effects
Dactinomycin / pharmacology
Down-Regulation / genetics
Epithelial Cells / cytology,  drug effects,  metabolism*
Gene Expression Regulation / drug effects,  physiology*
Genes, Reporter / genetics
Intercellular Adhesion Molecule-1 / genetics,  metabolism*
Interferon-gamma / pharmacology*
Jurkat Cells
MicroRNAs / antagonists & inhibitors,  physiology*
Mutation / genetics
Protein Biosynthesis / drug effects,  genetics
RNA, Small Interfering / genetics
STAT1 Transcription Factor / genetics
T-Lymphocytes / cytology
Transcription, Genetic / drug effects,  genetics
Up-Regulation / genetics
Grant Support
AI071321/AI/NIAID NIH HHS; R01 AI071321/AI/NIAID NIH HHS; R01 AI071321-01/AI/NIAID NIH HHS; R01 AI071321-02/AI/NIAID NIH HHS; R01 AI071321-03/AI/NIAID NIH HHS; R01 AI071321-04/AI/NIAID NIH HHS; R01 AI071321-05/AI/NIAID NIH HHS
Reg. No./Substance:
0/3' Untranslated Regions; 0/MIRN221 microRNA, human; 0/MicroRNAs; 0/RNA, Small Interfering; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 126547-89-5/Intercellular Adhesion Molecule-1; 1CC1JFE158/Dactinomycin; 82115-62-6/Interferon-gamma

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