| Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. | |
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MedLine Citation:
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PMID: 19890046 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rhinovirus (RV), a ssRNA virus of the picornavirus family, is a major cause of the common cold as well as asthma and chronic obstructive pulmonary disease exacerbations. Viral dsRNA produced during replication may be recognized by the host pattern recognition receptors TLR-3, retinoic acid-inducible gene (RIG)-I, and melanoma differentiation-associated gene (MDA)-5. No study has yet identified the receptor required for sensing RV dsRNA. To examine this, BEAS-2B human bronchial epithelial cells were infected with intact RV-1B or replication-deficient UV-irradiated virus, and IFN and IFN-stimulated gene expression was determined by quantitative PCR. The separate requirements of RIG-I, MDA5, and IFN response factor (IRF)-3 were determined using their respective small interfering RNAs (siRNA). The requirement of TLR3 was determined using siRNA against the TLR3 adaptor molecule Toll/IL-1R homologous region-domain-containing adapter-inducing IFN-beta (TRIF). Intact RV-1B, but not UV-irradiated RV, induced IRF3 phosphorylation and dimerization, as well as mRNA expression of IFN-beta, IFN-lambda1, IFN-lambda2/3, IRF7, RIG-I, MDA5, 10-kDa IFN-gamma-inducible protein/CXCL10, IL-8/CXCL8, and GM-CSF. siRNA against IRF3, MDA5, and TRIF, but not RIG-I, decreased RV-1B-induced expression of IFN-beta, IFN-lambda1, IFN-lambda2/3, IRF7, RIG-I, MDA5, and inflammatory protein-10/CXCL10 but had no effect on IL-8/CXCL8 and GM-CSF. siRNAs against MDA5 and TRIF also reduced IRF3 dimerization. Finally, in primary cells, transfection with MDA5 siRNA significantly reduced IFN expression, as it did in BEAS-2B cells. These results suggest that TLR3 and MDA5, but not RIG-I, are required for maximal sensing of RV dsRNA and that TLR3 and MDA5 signal through a common downstream signaling intermediate, IRF3. |
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Authors:
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Qiong Wang; Deepti R Nagarkar; Emily R Bowman; Dina Schneider; Babina Gosangi; Jing Lei; Ying Zhao; Christina L McHenry; Richai V Burgens; David J Miller; Umadevi Sajjan; Marc B Hershenson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-11-04 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 183 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-20 Completed Date: 2009-12-22 Revised Date: 2013-04-25 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6989-97 Citation Subset: AIM; IM |
Affiliation:
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Department of Molecular and Integrative Physiology., University of Michigan, Ann Arbor, MI 48109, USA |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Cell Line DEAD-box RNA Helicases / biosynthesis, genetics, immunology* Epithelial Cells / immunology*, virology Gene Expression Humans Picornaviridae Infections / immunology* RNA, Double-Stranded / immunology RNA, Small Interfering Receptors, Pattern Recognition / biosynthesis, genetics, immunology Respiratory Mucosa / immunology*, virology Reverse Transcriptase Polymerase Chain Reaction Rhinovirus / immunology Signal Transduction / immunology Toll-Like Receptor 3 / biosynthesis, genetics, immunology* |
| Grant Support | |
ID/Acronym/Agency:
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82550//PHS HHS; HL81420/HL/NHLBI NIH HHS; R01 HL081420-01A1/HL/NHLBI NIH HHS; R01 HL081420-05/HL/NHLBI NIH HHS; R01 HL082550/HL/NHLBI NIH HHS; R01 HL082550-01/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Double-Stranded; 0/RNA, Small Interfering; 0/Receptors, Pattern Recognition; 0/TLR3 protein, human; 0/Toll-Like Receptor 3; EC 3.6.1.-/DDX58 protein, human; EC 3.6.1.-/DEAD-box RNA Helicases; EC 3.6.1.-/IFIH1 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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