| miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes. | |
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MedLine Citation:
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PMID: 20110463 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Guoku Hu; Ai-Yu Gong; Jun Liu; Rui Zhou; Caishu Deng; Xian-Ming Chen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-01-28 |
Journal Detail:
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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:
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Created Date: 2010-03-22 Completed Date: 2010-04-16 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G542-50 Citation Subset: IM |
Affiliation:
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Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, Nebraska 68178, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3' Untranslated Regions
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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 Humans 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 | |
ID/Acronym/Agency:
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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 |
| Chemical | |
Reg. No./Substance:
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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; 50-76-0/Dactinomycin; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
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