Rosiglitazone‐induced CD36 up‐regulation resolves inflammation by PPARγ and 5‐LO‐dependent pathways

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

关键词: stroke;    resolution;    lipoxin;    microglia;    phagocytosis;   

DOI  :  10.1189/jlb.0613326

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

PPARγ‐achievedneuroprotectioninexperimentalstrokehasbeenexplainedbytheinhibitionofinflammatorygenes,anactioninwhich5‐LO,Alox5,isinvolved.Inaddition,PPARγisknowntopromotetheexpressionofCD36,ascavengerreceptorthatbindslipoproteinsandmediatesbacterialrecognitionandalsophagocytosis.Asphagocyticclearanceofneutrophilsisarequisiteforresolutionoftheinflammatoryresponse,PPARγ‐inducedCD36expressionmighthelptolimitinflammatorytissueinjuryinstroke,aneffectinwhich5‐LOmightalsobeinvolved.Homogenates,sections,andcellularsuspensionswerepreparedfrombrainsofWTandAlox5−/−miceexposedtodistalpMCAO.BMMswereobtainedfromLys‐MCre+PPARγf/fandLys‐MCre−PPARγf/fmice.Stereologicalcountingofdouble‐immunofluorescence‐labeledbrainsectionsandFACSanalysisofcellsuspensionswasperformed.Invivoandinvitrophagocytosisofneutrophilsbymicroglia/macrophageswasanalyzed.PPARγactivationwithRSGinducedCD36expressioninresidentmicroglia.Thisprocesswasmediatedbythe5‐LOgene,whichisinducedinneuronsbyPPARγactivationandatleastbyoneofitsproducts—LXA4—whichinducedCD36independentlyofPPARγ.Moreover,CD36expressionhelpedresolutionofinflammationthroughphagocytosis,concomitantlytoneuroprotection.Basedonthesefindings,inadditiontoadirectmodulationbyPPARγ,weproposeinbrainaparacrinemodelbywhichproductsgeneratedbyneuronal5‐LO,suchasLXA4,increasethemicroglialexpressionofCD36andpromotetissuerepairinpathologieswithaninflammatorycomponent,suchasstroke...

【 授权许可】

CC BY