Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Estrogen anti‐inflammatory activity on human monocytes is mediated through cross‐talk between estrogen receptor ERα36 and GPR30/GPER1 | |
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...
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