Nucleotide receptor P2RX7 stimulation enhances LPS‐induced interferon‐β production in murine macrophages

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

关键词: IRF‐;    3;    extracellular ATP;    enhanceosome;    type I IFN;    endotoxin;   

DOI  :  10.1189/jlb.0712351

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

StimulationofP2RX7withextracellularATPpotentiatesnumerousLPS‐inducedproinflammatoryevents,includingcytokineinductioninmacrophages,butthemolecularmechanismsunderlyingthisprocessarenotwelldefined.AlthoughP2RX7ligationhasbeenproposedtoactivateseveraltranscriptionfactors,manyoftheLPS‐inducedmediatorsaffectedbyP2RX7activationarenotinducedbyP2RX7agonistsalone,suggestingacomplementaryroleforP2RX7intranscriptionalregulation.TypeIIFNproduction,whoseexpressionistightlycontrolledbymultipletranscriptionfactorsthatformanenhanceosome,iscriticalforresistanceagainstLPS‐containingbacteria.TheeffectofpurinergicreceptorsignalingonLPS‐dependenttypeIIFNisunknownandwouldbeofgreatrelevancetoadiversearrayofinflammatoryconditions.ThepresentstudydemonstratesthatstimulationofmacrophageswithP2RX7agonistssubstantiallyenhancesLPS‐inducedIFN‐βexpression,andthisenhancementisablatedinmacrophagesthatdonotexpressfunctionalP2RX7orwhentheMAPKMEK1/2pathwaysareinhibited.PotentiationofLPS‐inducedIFN‐βexpressionfollowingP2RX7stimulationislikelytranscriptionallyregulated,asthisenhancementisobservedattheIFN‐βpromoterlevel.Furthermore,P2RX7stimulationisabletoincreasethephosphorylationandsubsequentIFN‐βpromoteroccupancyofIRF‐3,atranscriptionfactorthatiscriticalforIFN‐βtranscriptionbyTLRagonists.ThisnewlydiscoveredroleforP2RX7inIFNregulationmayhaveimplicationsinantimicrobialdefense,whichhasbeenlinkedtoP2RX7activationinotherstudies...

【 授权许可】

CC BY