Toll-like receptor mRNA expression is selectively increased in the colonic mucosa of two animal models relevant to irritable bowel syndrome
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Published Version
Date
2009-11-09
Authors
McKernan, Declan P.
Nolan, Aoife
Brint, Elizabeth K.
O'Mahony, Siobhain M.
Hyland, Niall P.
Cryan, John F.
Dinan, Timothy G.
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Published Version
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.
Description
Keywords
Toll-like receptors , Irritable bowel syndrome , Immunologic receptors
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