MicroRNA-146a is upregulated by and negatively regulates TLR2 signaling

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dc.contributor.authorQuinn, Edel M.
dc.contributor.authorWang, Jiang Huai
dc.contributor.authorO'Callaghan, Grace
dc.contributor.authorRedmond, H. Paul
dc.contributor.editorBereswill, Stefan
dc.date.accessioned2013-07-04T08:30:48Z
dc.date.available2013-07-04T08:30:48Z
dc.date.copyright2013
dc.date.issued2013-04-29
dc.description.abstractTLR signaling is a crucial component of the innate immune response to infection. MicroRNAs (miRNAs) have been shown to be upregulated during TLR signaling. Specifically, microRNA-146a (miR-146a) plays a key role in endotoxin tolerance by downregulating interleukin-1 receptor-associated kinase 1 (IRAK-1). The aim of this study was to assess the role of miR-146a in the TLR2 signaling and development of bacterial lipoprotein (BLP) self-tolerance and cross-tolerance to bacteria. Expression of miR-146a increased in a dose- and time-dependent manner in BLP-stimulated human THP-1 promonocytic cells. In BLP-tolerised cells miR-146a was even further upregulated in response to BLP re-stimulation (p,0.001). Restimulation of BLP-tolerised cells with heat-killed gram-negative Salmonella typhimurium (S. typhimurium), but not grampositive Staphylococcus aureus (S. aureus), led to significant overexpression of miR-146a (p,0.05). Transfection of naive cells with a miR-146a mimic substantially suppressed TNF-a production (p,0.05). Furthermore, overexpression of miR-146a resulted in strong reduction in IRAK-1 and phosphorylated IkBa expression in naive and S. typhimurium-stimulated THP-1 cells. Collectively, miR-146a is upregulated in response to BLP and bacterial stimulation in both naive and BLP-tolerised cells. Overexpression of miR-146a induces a state analogous to tolerance in BLP-stimulated cells and therefore may represent a future target for exogenous modulation of tolerance during microbial infection and sepsisen
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationQuinn EM, Wang JH, O’Callaghan G, Redmond HP (2013) MicroRNA-146a Is Upregulated by and Negatively Regulates TLR2 Signaling. PLoS ONE 8(4): e62232. doi:10.1371/journal.pone.0062232en
dc.identifier.doi10.1371/journal.pone.0062232
dc.identifier.issn1932-6203
dc.identifier.issued4en
dc.identifier.journaltitlePLOS Oneen
dc.identifier.startpagee62232en
dc.identifier.urihttps://hdl.handle.net/10468/1158
dc.identifier.volume8en
dc.language.isoenen
dc.publisherPLOS ONEen
dc.rights©2013 Quinn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en
dc.subjectTLR signalingen
dc.subjectMicroRNAsen
dc.subjectImmune response to infectionen
dc.titleMicroRNA-146a is upregulated by and negatively regulates TLR2 signalingen
dc.typeArticle (peer-reviewed)en
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