Novel Role for the Innate Immune Receptor Toll-Like Receptor 4 (TLR4) in the Regulation of the Wnt Signaling Pathway and Photoreceptor Apoptosis 英文参考文献.docVIP

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Novel Role for the Innate Immune Receptor Toll-Like Receptor 4 (TLR4) in the Regulation of the Wnt Signaling Pathway and Photoreceptor Apoptosis 英文参考文献.doc

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Novel Role for the Innate Immune Receptor Toll-Like Receptor 4 (TLR4) in the Regulation of the Wnt Signaling Pathway and Photoreceptor Apoptosis 英文参考文献

NovelRolefortheInnateImmuneReceptorToll-Like Receptor4(TLR4)intheRegulationoftheWntSignaling PathwayandPhotoreceptorApoptosis HyunYi1,AmitK.Patel1,ChhinderP.Sodhi2,DavidJ.Hackam2,AbigailS.Hackam1* 1BascomPalmerEyeInstitute,UniversityofMiamiMillerSchoolofMedicine,Miami,Florida,UnitedStatesofAmerica,2DepartmentofSurgery(Pediatric),Universityof Pittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Abstract Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations.Photoreceptorsarespecializedlight-detectingneuronsintheretinathatareessentialforvision.Inthis study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide(LPS)significantlyreducedthesurvivalofculturedmousephotoreceptorsexposedtooxidativestress. Withrespecttomechanism,TLR4suppressedWntsignaling,decreasedphosphorylationandactivationoftheWntreceptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protectedphotoreceptors,inaphenomenonknownaspreconditioning.ExpressionofTNFaanditsreceptorsTNFR1and TNFR2decreasedduringpreconditioning,andpreconditioningwasmimickedbyTNFaantagonists,butwasindependentof Wntsignaling.Therefore,TLR4isanovelregulatorofphotoreceptorsurvivalthatactsthroughtheWntandTNFapathways. Citation:YiH,PatelAK,SodhiCP,HackamDJ,HackamAS(2012)NovelRolefortheInnateImmuneReceptorToll-LikeReceptor4(TLR4)intheRegulationofthe WntSignalingPathwayandPhotoreceptorApoptosis.PLoSONE7(5):e36560.doi:10.1371/journal.pone.0036560 Editor:MauricioMartinsRodrigues,FederalUniversityofSa?o Paulo,Brazil ReceivedNovember29,2011;AcceptedApril7,2012;PublishedMay17,2012 Copyright:?2012Yietal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:Thisstudyw