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dc.contributor.authorParkinson, Nicholas J.en_US
dc.contributor.authorBuechner-Maxwell, Virginia A.en_US
dc.contributor.authorWitonsky, Sharon G.en_US
dc.contributor.authorPleasant, R. Scotten_US
dc.contributor.authorWerre, Stephen R.en_US
dc.contributor.authorAhmed, S. Ansaren_US
dc.date.accessioned2018-07-26T17:04:35Z
dc.date.available2018-07-26T17:04:35Z
dc.date.issued2017-05-26en_US
dc.identifier.othere0177664en_US
dc.identifier.urihttp://hdl.handle.net/10919/84406
dc.description.abstractThe innate immune response to lipopolysaccharide contributes substantially to the morbidity and mortality of gram-negative sepsis. Horses and humans share an exquisite sensitivity to lipopolysaccharide and thus the horse may provide valuable comparative insights into this aspect of the inflammatory response. MicroRNAs, small non-coding RNA molecules acting as post-transcriptional regulators of gene expression, have key roles in toll-like receptor signaling regulation but have not been studied in this context in horses. The central hypothesis of this study was that lipopolysaccharide induces differential microRNA expression in equine peripheral blood mononuclear cells in a manner comparable to humans. Illumina Next Generation Sequencing was used to characterize the basal microRNA transcriptome in isolated peripheral blood mononuclear cells from healthy adult horses, and to evaluate LPS-induced changes in microRNA expression in cells cultured for up to four hours. Selected expression changes were validated using quantitative reverse-transcriptase PCR. Only miR-155 was significantly upregulated by LPS, changing in parallel with supernatant tumor necrosis factor-α concentration. Eight additional microRNAs, including miR-146a and miR-146b, showed significant expression change with time in culture without a clear LPS effect. Target predictions indicated a number of potential immunity-associated targets for miR-155 in the horse, including SOCS1, TAB2 and elements of the PI3K signaling pathway, suggesting that it is likely to influence the acute inflammatory response to LPS. Gene alignment showed extensive conservation of the miR-155 precursor gene and associated promoter regions between horses and humans. The basal and LPS-stimulated microRNA expression pattern characterized here were similar to those described in human leukocytes. As well as providing a resource for further research into the roles of microRNAs in immune responses in horses, this will facilitate inter-species comparative study of the role of microRNAs in the inflammatory cascade during endotoxemia and sepsis.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.rightsAttribution 4.0en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleCharacterization of basal and lipopolysaccharide-induced microRNA expression in equine peripheral blood mononuclear cells using Next-Generation Sequencingen_US
dc.typeArticle - Refereeden_US
dc.description.versionPeer Revieweden_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0177664en_US
dc.identifier.volume12en_US
dc.identifier.issue5en_US
dc.type.dcmitypeTexten_US
dc.identifier.pmid28552958en_US
dc.identifier.eissn1932-6203en_US


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