Source:http://linkedlifedata.com/resource/pubmed/id/19596990
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2009-7-21
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pubmed:abstractText |
Upon recognition of viral components by pattern recognition receptors, including TLRs and retinoic acid-inducible gene I (RIG-I)- like helicases, cells are activated to produce type I IFN and proinflammatory cytokines. These pathways are tightly regulated by host to prevent inappropriate cellular response, but viruses can down-regulate these pathways for their survival. Recently, identification of negative regulators for cytoplasmic RNA-mediated antiviral signaling, especially the RIG-I pathway, attract much attention. However, there is no report about negative regulation of RIG-I antiviral pathway by microRNAs (miRNA) to date. We found that vesicular stomatitis virus (VSV) infection up-regulated miR-146a expression in mouse macrophages in TLR-myeloid differentiation factor 88-independent but RIG-I-NF-kappaB-dependent manner. In turn, miR-146a negatively regulated VSV-triggered type I IFN production, thus promoting VSV replication in macrophages. In addition to two known miR-146a targets, TRAF6 and IRAK1, we proved that IRAK2 was another target of miR-146a, which also participated in VSV-induced type I IFN production. Furthermore, IRAK1 and IRAK2 participated in VSV-induced type I IFN production by associating with Fas-associated death domain protein, an important adaptor in RIG-I signaling, in a VSV infection-inducible manner. Therefore, we demonstrate that miR-146a, up-regulated during viral infection, is a negative regulator of the RIG-I-dependent antiviral pathway by targeting TRAF6, IRAK1, and IRAK2.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DEAD-box RNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Ddx58 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1 Receptor-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Irak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/Mirn146 microRNA, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 6
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2150-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19596990-Animals,
pubmed-meshheading:19596990-DEAD-box RNA Helicases,
pubmed-meshheading:19596990-Feedback, Physiological,
pubmed-meshheading:19596990-Immunity,
pubmed-meshheading:19596990-Interferon Type I,
pubmed-meshheading:19596990-Interleukin-1 Receptor-Associated Kinases,
pubmed-meshheading:19596990-Macrophages,
pubmed-meshheading:19596990-Mice,
pubmed-meshheading:19596990-MicroRNAs,
pubmed-meshheading:19596990-TNF Receptor-Associated Factor 6,
pubmed-meshheading:19596990-Up-Regulation,
pubmed-meshheading:19596990-Vesicular Stomatitis,
pubmed-meshheading:19596990-Vesiculovirus,
pubmed-meshheading:19596990-Virus Diseases,
pubmed-meshheading:19596990-Virus Replication
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pubmed:year |
2009
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pubmed:articleTitle |
MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2.
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pubmed:affiliation |
Institute of Immunology, Tsinghua University School of Medicine, Beijing, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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