Toll-like receptor mRNA expression is selectively increased in the colonic mucosa of two animal models relevant to irritable bowel syndrome
| dc.contributor.author | McKernan, Declan P. | |
| dc.contributor.author | Nolan, Aoife | |
| dc.contributor.author | Brint, Elizabeth K. | |
| dc.contributor.author | O'Mahony, Siobhain M. | |
| dc.contributor.author | Hyland, Niall P. | |
| dc.contributor.author | Cryan, John F. | |
| dc.contributor.author | Dinan, Timothy G. | |
| dc.contributor.funder | Science Foundation Ireland | en |
| dc.contributor.funder | GlaxoSmithKline, United Kingdom | en |
| dc.date.accessioned | 2010-02-08T13:40:29Z | |
| dc.date.available | 2010-02-08T13:40:29Z | |
| dc.date.issued | 2009-11-09 | |
| dc.description.abstract | Background: 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.sponsorship | Science Foundation Ireland (Centre for Science and Technology (CSET)); GlaxoSmithKline, United Kingdom | en |
| dc.description.status | Peer reviewed | en |
| dc.description.version | Published Version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | McKernan 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.0008226 | en |
| dc.identifier.doi | 10.1371/journal.pone.0008226 | |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.issued | 12 | en |
| dc.identifier.journaltitle | PLoS ONE | en |
| dc.identifier.startpage | e8226 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/111 | |
| dc.identifier.volume | 4 | en |
| dc.language.iso | en | en |
| dc.publisher | Public Library of Science | en |
| dc.rights | ©2009 McKernan et al. | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ | en |
| dc.subject | Toll-like receptors | en |
| dc.subject | Irritable bowel syndrome | en |
| dc.subject | Immunologic receptors | en |
| dc.subject.lcsh | Gastrointestinal system -- Diseases | en |
| dc.title | Toll-like receptor mRNA expression is selectively increased in the colonic mucosa of two animal models relevant to irritable bowel syndrome | en |
| dc.type | Article (peer-reviewed) | en |
