Specificity of eicosanoid production depends on the TLR‐4‐stimulated macrophage phenotype

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

关键词: lipidomics;    prostaglandin;    cyclooxygenase;    metabolism;    coupling;    synthase;   

DOI  :  10.1189/jlb.0311153

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Eicosanoidmetabolismdiffersinprofileandquantitybetweenmacrophagesofdifferenttissueoriginandmethodofelicitation,aswellasbetweenprimaryandimmortalizedmacrophagesafteractivationwithinflammatorystimuli.Usingalipidomicapproach,wecomprehensivelyanalyzedtheeicosanoidsmadebymurineRPMs,TGEMs,BMDM,andthemacrophage‐likecelllineRAWafterstimulationwiththeTLR‐4‐specificagonistKLA.DirectcorrelationamongtotalCOXmetabolites,COXside‐products(11‐HETE,15‐HETE),COX‐2mRNA,andproteinat8hwasfoundwhencomparingeachcelltype.ComprehensiveqPCRanalysiswasusedtocomparerelativetranscriptlevelsbetweentheterminalprostanoidsynthasesthemselvesaswellasbetweeneachcelltype.LevelsofPGE2,PGD2,andTxB2generallycorrelatedwithenzymetranscriptexpressionofPGES,PGDS,andTBXS,providingevidenceofcomparableenzymeactivities.PGIStranscriptwasexpressedonlyinRPMandTGEMmacrophagesandatanexceptionallylowlevel,despitehighmetaboliteproductioncomparedwithothersynthases.PresenceofPGISinRPMandTGEMalsoloweredtheproductionofPGE2versusPGD2byapproximatelytenfoldrelativetoBMDMandRAWcells,whichlackedthisenzyme.OurresultsdemonstratethatdelayedPGproductiondependsonthemaximallevelofCOX‐2expressionindifferentmacrophagesafterTLR‐4stimulation.Also,thesameenzymesineachcelllargelydictatetheprofileofeicosanoidsproduceddependingontheratiosofexpressionbetweenthem,withtheexceptionofPGIS,whichappearstohavemuchgreatersyntheticcapacityandcompetesselectivelywithmPGES‐1...

【 授权许可】

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