| Abstract: | BackgroundThe irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whosepathogenesis is not completely understood. Its high prevalence and the considerableeffects on quality of life make IBS a disease with high social cost. Recent studiessuggest that low grade mucosal immune activation, increased intestinal permeability andthe altered host-microbiota interactions that modulate innate immune response,contribute to the pathophysiology of IBS. However, the understanding of the precisemolecular pathophysiology remains largely unknown.Methodology and FindingsIn this study our objective was to evaluate the TLR expression as a key player in theinnate immune response, in the colonic mucosa of IBS patients classified into the threemain subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expressionwas assessed by real time RT-PCR while TLRs protein expression in intestinal epithelialcells was specifically assessed by flow cytometry and immunofluorescence. Mucosalinflammatory cytokine production was investigated by the multiplex technology. Here wereport that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 andTLR4 in the colonic mucosa. Furthermore, these expressions were localized in theepithelial cells, opening new perspectives for a potential role of epithelial cells inhost-immune interactions in IBS. In addition, the increased TLR expression in IBS-Mpatients elicited intracellular signaling pathways resulting in increased expression ofthe mucosal proinflammatory cytokines IL-8 and IL1β.ConclusionsOur results provide the first evidence of differential expression of TLR in IBSpatients according to the disease subtype. These results offer further support thatmicroflora plays a central role in the complex pathophysiology of IBS providing novelpharmacological targets for this chronic gastrointestinal disorder according to bowelhabits. |
