Toll-like receptors may point to immune changes in IBS
MedWire News: Individuals with irritable bowel syndrome (IBS) have alterations in levels of toll-like receptors (TLRs) that suggest the innate immune system plays a role in the pathogenesis of the syndrome, conclude investigators.
Despite several pathophysiological mechanisms having been proposed for IBS, there is no one single unifying hypothesis. Recent studies have revealed that IBS is linked to low-grade immune activation in some patients. Again, the underlying cause is unclear.
TLRs, which are pattern-recognition receptors, have an important role in the mucosal innate immune response. Elizabeth Brint, from Cork University Hospital in Ireland, and colleagues therefore investigated the expression of TLRs in colonic biopsy samples obtained from 26 IBS patients and 19 healthy individuals.
Specifically, they performed microarray analysis on nine IBS patients and eight healthy controls, along with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) on colonic biopsy samples obtained from 26 female IBS patients, 19 healthy controls, 10 ulcerative colitis patients and 19 Crohn's disease patients.
In addition, immunofluorescence was used to determine protein expression of TLR4, TLR7, and TLR8, and western blot to assess alterations in the TLR4 protein, in the samples from IBS patients and healthy controls.
On microarray analysis, there was a significant 1.4-fold increase in TLR4 expression in IBS patients versus healthy controls. On RT-PCR, IBS patients had significant increases in TLR4 and TLR5 expression compared with healthy controls, while expression of TLR7 and TLR8 was significantly decreased by approximately 50% in IBS patients.
The team notes in the American Journal of Gastroenterology that the increase in TLR4 expression in IBS patients was approximately five fold, compared with increases of approximately 15-fold and eight fold in ulcerative colitis and Crohn's disease patients, respectively.
Protein expression for TLR4, TLR7, and TLR8 was strongest in the crypts and at the luminal surface on immunofluorescence, and Western blotting confirmed the increases in TLR4 expression. Interestingly, there were no underlying alterations in TLR regulatory proteins, indicating that these were not responsible for the overall immune changes.
The team writes: "The differences we have observed may indicate an appropriate immune response to a pathogen or to alterations in the host microbiota.
"In particular, these data direct attention to the microbial composition of the gut as a potential modifier or contributor to the inflammation."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Liam Davenport