N‐Octanoyl dopamine transiently inhibits T cell proliferation via G1 cell‐cycle arrest and inhibition of redox‐dependent transcription factors

[摘要] Recently,wedevelopedanonhemodynamicdopaminederivative,NOD,whichhasprofoundanti‐inflammatoryeffectsinvitro.AsNODalsoprotectsratsfromischemicAKI,thepresentstudytestedwhetherNODisabletomodulatecellularimmunityforpotentialuseasaTcell‐suppressiveagent.Tothisend,Tcellswerestimulatedbyanti‐CD3/CD28orPMA/ionomycininthepresenceorabsenceofdifferentconcentrationsofNOD.Tcellproliferation,activationmarkers,intracellularcytokineexpression,andactivationoftranscriptionfactorswereassessed.WhereasTcellproliferationwasinhibitedsignificantlybyNODatDay3,proliferationwasrestoredatDay7orlaterdependingontheNODconcentrationused.InhibitionofproliferationwasreflectedbyadiminishedCD25expressionandswitchfromnaivetomemoryTcells.EarlyTCRactivationeventswereunaffected,yetNF‐κBandAP‐1werestronglyinhibitedbyNOD.TheinhibitoryeffectofNODseemedtobedependentonitsredoxactivity,asNOT,aredox‐inactiveNODderivate,didnotinfluenceproliferation.NODdisplayedsynergisticeffectswithCNIsonTcellproliferation.OurdatademonstratethatNODdisplaysTcell‐suppressiveactivity.Inkeepingwithitsanti‐inflammatoryactionanditsbeneficialeffectonischemia‐inducedAKI,NODmaybeaninterestingdrugcandidatetopreventCNI‐relatedside‐effects...

[学科分类] 生理学

[关键词] T lymphocytes;NF‐κB;AP‐1;immunosuppression;transplantation;N‐acyl dopamine