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1、HostResponsestoIntestinalMicrobialAntigensinGluten-SensitiveMice111123JaneM.Natividad,XianxiHuang,EmmaSlack,JenniferJury,YolandaSanz,ChellaDavid,1451.1.EmmanuelDenou,PinchangYang,JosephMurray,KathyD.McCoy,ElenaF.Verdu´*1FarncombeFamilyDigestiveHealthR
2、esearchInstitute,McMasterUniversity,Hamilton,Canada,2InstituteofAgrochemistryandFoodTechnology(IATA),SpanishNationalResearchCouncil(CSIC),Valencia,Spain,3DepartmentofImmunology,MayoClinic,Rochester,Minnesota,UnitedStatesofAmerica,4DepartmentofPatholog
3、y,McMasterUniversity,Hamilton,Canada,5DivisionofGastroenterology,MayoClinic,Rochester,Minnesota,UnitedStatesofAmericaAbstractBackgroundandAims:Excessiveuptakeofcommensalbacterialantigensthroughapermeableintestinalbarriermayinfluencehostresponsestospec
4、ificantigeninageneticallypredisposedhost.Theaimofthisstudywastoinvestigatewhetherintestinalbarrierdysfunctioninducedbyindomethacintreatmentaffectsthehostresponsetointestinalmicrobiotaingluten-sensitizedHLA-DQ8/HCD4mice.Methodology/PrincipalFindings:HL
5、A-DQ8/HCD4miceweresensitizedwithgluten,andgavagedwithindomethacinplusgluten.IntestinalpermeabilitywasassessedbyUssingchamber;epithelialcell(EC)ultra-structurebyelectronmicroscopy;RNAexpressionofgenescodingforjunctionalproteinsbyQ-real-timePCR;immunere
6、sponsebyin-vitroantigen-specificT-cellproliferationandcytokineanalysisbycytometricbeadarray;intestinalmicrobiotabyfluorescenceinsituhybridizationandanalysisofsystemicantibodiesagainstintestinalmicrobiotabysurfacestainingoflivebacteriawithserumfollowed
7、byFACSanalysis.Indomethacinledtoamorepronouncedincreaseinintestinalpermeabilityingluten-sensitizedmice.ThesechangeswereaccompaniedbysevereECdamage,decreasedE-cadherinRNAlevel,elevatedIFN-cinsplenocyteculturesupernatant,andproductionofsignificantIgMant
8、ibodyagainstintestinalmicrobiota.Conclusion:IndomethacinpotentiatesbarrierdysfunctionandECinjuryinducedbygluten,affectssystemicIFN-cproductionandthehostresponsetointestinalmicrobiotaantigensinHLA-DQ8/HCD4mice.Theresultssuggestthatenvironmental
