G‐CSF‐activated STAT3 enhances production of the chemokine MIP‐2 in bone marrow neutrophils

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

关键词: chemotaxis;    transcription;    chromatin;   

DOI  :  10.1189/jlb.0312126

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophilmobilizationfromthebonemarrowisacriticalaspectoftheinnateimmuneresponse,enablingarapiddeploymentofphagocytestoinfectedorinflamedtissue.ThecytokineG‐CSF,whichisinducedrapidlyduringinfection,elicitsaswiftandpotentmobilizingresponse,yetitsmechanismsofactionremainpoorlyunderstood.Here,westudiedtheroleofG‐CSFanditsprincipalsignaltransducerSTAT3inregulatingexpressionoftheneutrophilchemoattractantMIP‐2.OurstudiesrevealedGr‐1himatureneutrophilsasmajorsourcesofCxcl2(MIP‐2)mRNAinbonemarrowandG‐CSF‐responsiveMIP‐2proteinproduction.InductionofCxcl2wasregulateddirectlybyG‐CSF‐activatedSTAT3viainteractionataSTATconsensuselementintheCxcl2promoter.G‐CSFcoordinatelystimulatedtheassociationofSTAT3,inductionofthetranscriptionallyactiveH3K4me3modification,andrecruitmentofRNAPolIIattheCxcl2proximalpromoter,aswellasthepromoterregionofIl8rb,encodingtheMIP‐2receptor.TheseresultssuggestthattheG‐CSF–STAT3pathwaydirectlyregulatestranscriptionaleventsthatinduceneutrophilmobilization...

【 授权许可】

CC BY