Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF- B Translocation in a Mechanism Independent of Plasmodium Killing英文文献资料.docVIP

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Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF- B Translocation in a Mechanism Independent of Plasmodium Killing英文文献资料.doc

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Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF- B Translocation in a Mechanism Independent of Plasmodium Killing英文文献资料

HindawiPublishingCorporation MalariaResearchandTreatment Volume2012,ArticleID679090,12pages doi:10.1155/2012/679090 ResearchArticle ArtesunateExertsaDirectEffectonEndothelial CellActivationandNF-κBTranslocationinaMechanism IndependentofPlasmodiumKilling MarianaC.Souza, 1Fl′avioHenriqueMarcolinoPaix?ao,1,2FaustoK.Ferraris,1 IsabelaRibeiro, andMariadasGrac?asM.O.Henriques 1 3 1 2 3 Laborat′oriodeFarmacologiaAplicada,DepartamentodeFarmacologiaAplicada,Farmanguinhos,Fundac??aoOswaldoCruz, RuaSizenandoNabuco100,Manguinhos,21041-250RiodeJaneiro,RJ,Brazil Laborat′oriodeEducac??aoPro?ssionalemT′ecnicasLaboratoriaisemSa′ude,EscolaPolit′ecnicadeSa′udeJoaquimVen?ancio, Fundac??aoOswaldoCruz,RiodeJaneiro,RJ,Brazil DrugsforNeglectedDiseasesInitiative,Geneva,Switzerland CorrespondenceshouldbeaddressedtoMariadasGrac?asM.O.Henriques,gracahenriques@?ocruz.br Received30May2012;Revised16August2012;Accepted30August2012 AcademicEditor:MatsWahlgren Copyright?2012MarianaC.Souzaetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities.Fewstudieshaveaddressedthee?ectofartesunateinthemurinemalariamodeloritse?ectonhostimmuneresponse duringmalariainfection.Herein,westudythee?ectofartesunatetreatmentanddescribeanauxiliarymechanismofartesunate in modulating the in?ammatory response during experimental malaria infection in mice. Treatment with artesunate did not reducesigni?cantlytheparasitemiawithin12h,however,reducedBBBbreakdownandTNF-αmRNAexpressioninthebrain tissueofartesunate-treatedmice.Conversely,me?oquinetreatmentwasnotabletoalterclinicalfeatures.Notably,artesunate pretreatmentfailedtomodulatetheexpressionofLFA-1insplenocytesstimulatedwithparasitizedredbloodcells(pRBCs)invitro; however,itabrogatedtheexpressionof