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


RESULTS
In this study, our objective was to evaluate the TLR expression profile in the colonic mucosa of two rat strains that display colonic visceral hypersensitivity; 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.
McKernan
Declan P
DP
Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Nolan
Aoife
A
Brint
Elizabeth K
EK
O'Mahony
Siobhain M
SM
Hyland
Niall P
NP
Cryan
John F
JF
Dinan
Timothy G
TG
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D051193:Toll-Like Receptors / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D051193:Toll-Like Receptors