Role of Toll Like Receptors in Irritable Bowel Syndrome Differential Mucosal Immune Activation According to the Disease Subtype 英文参考文献.docVIP

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Role of Toll Like Receptors in Irritable Bowel Syndrome Differential Mucosal Immune Activation According to the Disease Subtype 英文参考文献.doc

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Role of Toll Like Receptors in Irritable Bowel Syndrome Differential Mucosal Immune Activation According to the Disease Subtype 英文参考文献

RoleofTollLikeReceptorsinIrritableBowelSyndrome: DifferentialMucosalImmuneActivationAccordingtothe DiseaseSubtype LilianaBelmonte1,2,3*,Ste′phanieBeutheuYoumba1,2,NathalieBertiaux-Vandae¨le4,MichelAntonietti4, Ste′phaneLecleire1,2,4,AlbertoZalar4,GuillaumeGourcerol1,2,5,Anne-MarieLeroi1,2,5 PierreDe′chelotte1,2,6,Mo?¨seCoe¨ffier1,2,6,PhilippeDucrotte′1,2,4 , 1INSERM Unit U1073, Rouen University, Rouen, France, 2Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France, 3Laboratory of Immunology, IIHema, Consejo Nacional de Investigaciones Cient?′ficas y Te′cnicas, Academy National of Medicine, Buenos Aires, Argentine, 4Gastroenterology Department,RouenUniversityHospital,Rouen,France,5PhysiologyDepartment,RouenUniversityHospital,Rouen,France,6NutritionUnit,RouenUniversityHospital, Rouen,France Abstract Background: The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost.Recentstudiessuggestthat lowgrademucosal immuneactivation,increased intestinalpermeabilityandthe altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However,theunderstandingoftheprecisemolecularpathophysiologyremainslargelyunknown. MethodologyandFindings:InthisstudyourobjectivewastoevaluatetheTLRexpressionasakeyplayerintheinnate immuneresponse,inthecolonicmucosaofIBSpatientsclassifiedintothethreemainsubtypes(withconstipation,with diarrheaor mixed).TLR2 andTLR4 mRNAexpressionwas assessed byreal timeRT-PCR whileTLRs proteinexpressionin intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokineproductionwasinvestigatedbythemultiplextechnology.HerewereportthattheIBS-Mixedsubgroupdisplayeda significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore,