Toll-like receptor mRNA expression is selectively increased in the colonic mucosa of two animal models relevant to irritable bowel syndrome

dc.contributor.authorMcKernan, Declan P.
dc.contributor.authorNolan, Aoife
dc.contributor.authorBrint, Elizabeth K.
dc.contributor.authorO'Mahony, Siobhain M.
dc.contributor.authorHyland, Niall P.
dc.contributor.authorCryan, John F.
dc.contributor.authorDinan, Timothy G.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderGlaxoSmithKline, United Kingdomen
dc.description.abstractBackground: Irritable bowel syndrome (IBS) is largely viewed as a stress-related disorder caused by aberrant brain-gut– immune communication and altered gastrointestinal (GI) homeostasis. Accumulating evidence demonstrates that stress modulates innate immune responses; however, very little is known on the immunological effects of stress on the GI tract. Toll-like receptors (TLRs) are critical pattern recognition molecules of the innate immune system. Activation of TLRs by bacterial and viral molecules leads to activation of NF-kB and an increase in inflammatory cytokine expression. It was our hypothesis that innate immune receptor expression may be changed in the gastrointestinal tract of animals with stressinduced IBS-like symptoms. Methodology/Principal Findings: In this study, our objective was to evaluate the TLR expression profile in the colonic mucosa of two rat strains that display colonic visceral hypersensivity; the stress-sensitive Wistar-Kyoto (WKY) rat and the maternally separated (MS) rat. Quantitative PCR of TLR2-10 mRNA in both the proximal and distal colonic mucosae was carried out in adulthood. Significant increases are seen in the mRNA levels of TLR3, 4 & 5 in both the distal and proximal colonic mucosa of MS rats compared with controls. No significant differences were noted for TLR 2, 7, 9 & 10 while TLR 6 could not be detected in any samples in both rat strains. The WKY strain have increased levels of mRNA expression of TLR3, 4, 5, 7, 8, 9 & 10 in both the distal and proximal colonic mucosa compared to the control Sprague-Dawley strain. No significant differences in expression were found for TLR2 while as before TLR6 could not be detected in all samples in both strains. Conclusions: These data suggest that both early life stress (MS) and a genetic predisposition (WKY) to stress affect the expression of key sentinels of the innate immune system which may have direct relevance for the molecular pathophysiology of IBS.en
dc.description.sponsorshipScience Foundation Ireland (Centre for Science and Technology (CSET)); GlaxoSmithKline, United Kingdomen
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.identifier.citationMcKernan DP, Nolan A, Brint EK, O’Mahony SM, Hyland NP, et al. (2009) Toll-Like Receptor mRNA Expression Is Selectively Increased in the Colonic Mucosa of Two Animal Models Relevant to Irritable Bowel Syndrome. PLoS ONE 4(12): e8226. doi:10.1371/journal.pone.0008226en
dc.identifier.journaltitlePLoS ONEen
dc.publisherPublic Library of Scienceen
dc.rights©2009 McKernan et al.en
dc.subjectToll-like receptorsen
dc.subjectIrritable bowel syndromeen
dc.subjectImmunologic receptorsen
dc.subject.lcshGastrointestinal system -- Diseasesen
dc.titleToll-like receptor mRNA expression is selectively increased in the colonic mucosa of two animal models relevant to irritable bowel syndromeen
dc.typeArticle (peer-reviewed)en
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