The carotenoid lutein enhances matrix metalloproteinase‐9 production and phagocytosis through intracellular ROS generation and ERK1/2, p38 MAPK, and RARβ activation in murine macrophages

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

关键词: lycopene;    MMP;    Nox;    p47 phox;    retinoic acid receptor;    nuclear receptor;   

DOI  :  10.1189/jlb.0512238

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Earlystudieshavedemonstratedtheabilityofdietarycarotenoidstoenhanceimmuneresponse,butthemechanismunderlyingtheirinfluenceonmacrophageactivityremainsunclear.Here,weinvestigatedtheeffectsofcarotenoidsonmacrophageactivity.Carotenoids,includingluteinandlycopene,enhancedMMP‐9activityinRAW264.7macrophages.Luteinwaschosenasarepresentativeandanalyzedfurtherinthisstudy.Itincreasedthesynthesis,activity,andreleaseofMMP‐9inmurineRAW264.7andprimary‐culturedperitonealmacrophages.MMP‐9inductionbyluteinwasthroughthetranscriptionalregulationofmmp‐9.ItwasbluntedbytheMAPKinhibitorstargetingERK1/2andp38MAPK,thereagentsthatinhibitfreeradicalsignaling,andtheinhibitorsandsiRNAtargetingRARβ.Moreover,luteininducedNoxactivationandintracellularROSproductionatanearlystageoftreatment.ThiscarotenoidalsocausedERK1/2andp38MAPKactivation,RARβexpression,andRARinteractionwithitsresponsiveelementinthepromoterregion.ThesefindingssuggesttheinvolvementofROS,MAPKs,andRARβactivationinlutein‐drivenMMP‐9expressionandrelease.Interestingly,luteinenhancedthephagocyticactivityofmacrophages,andthesecretedMMP‐9appearedtobeinvolvedinthisprocess.Insummary,weprovideevidencehereforthefirsttimethatthecarotenoidluteininducesintracellularROSgenerationandMAPKandRARβactivationinmacrophages,leadingtoanincreaseinMMP‐9releaseandmacrophagephagocytosis.Ourresultsdemonstratethatluteinexertsanimmunomodulatoryeffectonmacrophages...

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