FcεR1-Mediated Mast Cell Reactivity Is Amplified through Prolonged Toll-Like Receptor-Ligand Treatment 英文参考文献.docVIP

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FcεR1-Mediated Mast Cell Reactivity Is Amplified through Prolonged Toll-Like Receptor-Ligand Treatment 英文参考文献.doc

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FcεR1-Mediated Mast Cell Reactivity Is Amplified through Prolonged Toll-Like Receptor-Ligand Treatment 英文参考文献

FceR1-MediatedMastCellReactivityIsAmplifiedthrough ProlongedToll-LikeReceptor-LigandTreatment RohitSaluja1,IngridDelin2,GunnarP.Nilsson1,3*.,MikaelAdner2,3. 1ClinicalImmunologyandAllergyUnit,DepartmentofMedicine,KarolinskaInstitutet,Stockholm,Sweden,2ExperimentalAsthmaandAllergyResearch,TheInstituteof EnvironmentalMedicine,KarolinskaInstitutet,Stockholm,Sweden,3TheCentreforAllergyResearch,KarolinskaInstitutet,Stockholm,Sweden Abstract Background: Mast cell-derived mediators mediate several of the pathological features of asthma. Microbial infections induceasthmaexacerbationsinwhichthecontributionofmastcellsremainsincomprehensible. PrincipalFindings:InthisstudywehaveinvestigatedthecharacteristicexpressionpatternofToll-likereceptors(TLRs)1–9 andtheeffectofTLRligandtreatmentonIgE-receptormediatedmastcellreactivity.Forthestudiesweemployedinvitro differentiatedconnectivetissuelikemastcells(CTLMC)andmucosallikemastcells(MLMC)frommice.Bothphenotypes were treated for 24h or 96h with ligands for TLR1/2, TLR2/6, TLR3 and TLR4, before activation with IgE and antigen. Prolongedexposure(96h)withTLR-ligandspromotedmastcellreactivityfollowingIgE-receptoractivation.TLR4activation withLPSgeneratedthemostpronouncedeffect,withanenhanceddegranulationandsecretionofleukotrienes,cytokines andchemokines,inbothCTLMCandMLMC.TheeffectofLPSwasmediatedthroughaMyd88-dependentpathwayandthe increasedeffectinvolvedJNK-dependentpathway. Conclusion:Wefindthatprolongedexposureofmastcellstopathogens/TLR-ligandsmodulatestheireffectorresponsesby primingthemforincreasedreleaseofseveralinflammatorymediatorswhensubsequentlyactivatedbyIgE-receptors.These datasuggestthatinfectionsmightexaggeratetheseverityofallergicreactionssuchasinasthma,byenhancingmediator releasefrommastcells. Citation: Saluja R, Delin I, Nilsson GP, Adner M (2012) FceR1-Mediated Mast Cell Reactivity Is Amplified through Prolonged Toll-Like Receptor-Ligand Treatment.PLoSONE7(8):e43547.doi:10.1371/journal.pone.0043547 Editor:NickGay,Unive