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

[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...

[学科分类] 生理学

[关键词] ROS;phagocyte;NOX2;p47phox;proline isomerase