E‐prostanoid 2 receptors dampen mast cell degranulation via cAMP/PKA‐mediated suppression of IgE‐dependent signaling

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: Butaprost calcium;    Fcɛ;    I;    Fyn;    PGE2 ;   

DOI  :  10.1189/jlb.0212109

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheexperimentaladministrationofPGE2forthetreatmentofasthmadampensclinicalsymptoms,andsimilarefficacyhasbeenfoundindustmite‐inducedhypersensitivityreactionsinanimalmodels.Here,weinvestigatethemechanismbywhichPGE2mediatessuppressionofMCdegranulation.WefindthattheeffectofPGE2onFcɛRI‐dependentMCdegranulationvariesfromactivatingtosuppressing,dependingontherelativeratioofEP2toEP3expressiononthesecellswithsuppressionevidentonlyincellshavingincreasedEP2toEP3expression.ConsistentwitharoleforEP2insuppressingMCresponsesinvitro,wefoundthataselectiveEP2agonist,Butaprost,inhibitedMC‐mediatedFcɛRI‐inducedimmediatehypersensitivityinamodelofPCA.EP2engagementonMCsincreasedcAMPproductionandinhibitedFcɛRI‐mediatedcalciuminflux.Inaddition,italsodecreasedtheextentofFcɛRI‐inducedFynkinaseactivity,leadingtodecreasedphosphorylationofkeysignalingmoleculessuchasGab2andAkt.TreatmentwithanantagonistofcAMPorshRNAdown‐regulationofPKA(theprincipalintracellulartargetofcAMP)reversedtheEP2‐mediatedinhibitoryeffectonMCdegranulationandrestoredcalciuminfluxandphosphorylationofAkt.Collectively,thefindingsdemonstratethatEP2suppressestheFyn‐mediatedsignalsthatarecentraltoFcɛRI‐dependentMCdegranulation,suggestingthatengagementoftheEP2onMCsmaybebeneficialindampeningallergicresponses...

【 授权许可】

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