Estrogen anti‐inflammatory activity on human monocytes is mediated through cross‐talk between estrogen receptor ERα36 and GPR30/GPER1

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

关键词: macrophages;    IL‐;    6;    NF‐;    κ;    B;    atherosclerosis;   

DOI  :  10.1189/jlb.3A0914-430RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Estrogensareknownmodulatorsofmonocyte/macrophagefunctions;however,theunderlyingmechanismhasnotbeenclearlydefined.Recently,anumberofestrogenreceptormoleculesandsplicevariantswereidentifiedthatexertdifferentandsometimesopposingactions.Weassessedtheexpressionofestrogenreceptorsandexploredtheirroleinmediatingestrogenicanti‐inflammatoryeffectsonhumanprimarymonocytes.Wereportthattheonlyestrogenreceptorsexpressedareestrogenreceptor‐α36‐kDasplicevariantandG‐proteincoupledreceptor30/G‐proteinestrogenreceptor1,inasex‐independentmanner.17‐β‐EstradiolinhibitstheLPS‐inducedIL‐6inflammatoryresponse,resultingininhibitionofNF‐κBtranscriptionalactivity.Thisisachievedviaadirectphysicalinteractionofligand‐activatedestrogenreceptor‐α36‐kDasplicevariantwiththep65componentofNF‐κBinthenucleus.G‐proteincoupledreceptor30/G‐proteinestrogenreceptor1,whichalsophysicallyinteractswithestrogenreceptor‐α36‐kDasplicevariant,actsacoregulatorinthisprocess,becauseitsinhibitionblockstheeffectofestrogensonIL‐6expression.However,itsactivationdoesnotmimictheeffectofestrogens,onneitherIL‐6norNF‐κBactivity.Finally,weshowthattheestrogenreceptorprofileobservedinmonocytesisnotmodifiedduringtheirdifferentiationtomacrophagesordendriticcellsinvitroandissharedinvivobymacrophagespresentinatheroscleroticplaques.Theseresultspositionestrogenreceptor‐α36‐kDasplicevariantandG‐proteincoupledreceptor30asimportantplayersandpotentialtherapeutictargetsinmonocyte/macrophage‐dependentinflammatoryprocesses...

【 授权许可】

CC BY