TLR8, but not TLR7, induces the priming of the NADPH oxidase activation in human neutrophils

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

关键词: ROS;    phagocyte;    NOX2;    p47phox;    proline isomerase;   

DOI  :  10.1189/jlb.2A1214-623R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophilsplayakeyroleinhostdefenseagainstinvadingpathogensbyreleasingtoxicagents,suchasROSandantimicrobialpeptides.HumanneutrophilsexpressseveralTLRsthatrecognizeavarietyofmicrobialmotifs.TheinteractionbetweenTLRandtheiragonistsisbelievedtohelpneutrophilstorecognizeandtokillpathogensefficientlybyincreasingtheiractivation,aprocesscalledpriming.However,excessiveactivationcaninducetissueinjuryandthereby,contributetoinflammatorydisorders.AgoniststhatactivateTLR7andTLR8induceprimingofneutrophilROSproduction;however,whichreceptorisinvolvedinthisprocesshasnotbeenelucidated.Inthisstudy,weshowthattheselectiveTLR8agonist,CL075(3M002),inducedadramaticincreaseoffMLF‐stimulatedNOX2activation,whereastheselectiveTLR7agonist,loxoribine,failedtoinduceanyprimingeffect.Interestingly,CL075,butnotloxoribine,inducedthephosphorylationoftheNOX2cytosoliccomponentp47phoxonseveralserinesandthephosphorylationofp38MAPKandERK1/2.Theinhibitorofp38MAPKcompletelyblockedCL075‐inducedphosphorylationofp47phoxSer345.Moreover,CL075,butnotloxoribine,inducedtheactivationoftheprolineisomerasePin1,andjuglone,aPin1inhibitor,preventedCL075‐mediatedprimingoffMLF‐inducedsuperoxideproduction.TheseresultsindicatethatTLR8,butnotTLR7,isinvolvedinprimingofhumanneutrophilROSproductionbyinducingthephosphorylationofp47phoxandp38MAPKandthatPin1isalsoinvolvedinthisprocess...

【 授权许可】

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