NLRP3 Inflammasome Key Mediator of Neuroinflammation in Murine Japanese Encephalitis 英文参考文献.docVIP

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NLRP3 Inflammasome Key Mediator of Neuroinflammation in Murine Japanese Encephalitis 英文参考文献.doc

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NLRP3 Inflammasome Key Mediator of Neuroinflammation in Murine Japanese Encephalitis 英文参考文献

NLRP3Inflammasome:KeyMediatorof NeuroinflammationinMurineJapaneseEncephalitis DeepakKumarKaushik*.,MalvikaGupta.,KanhaiyaLalKumawat,AnirbanBasu NationalBrainResearchCentre,Manesar,Haryana,India Abstract Background:JapaneseEncephalitisvirus(JEV)isacommoncauseofacuteandepidemicviralencephalitis.JEVinfectionis associatedwithmicroglialactivationresultingintheproductionofpro-inflammatorycytokinesincludingInterleukin-1b(IL- 1b)andInterleukin-18(IL-18).ThePatternRecognitionReceptors(PRRs)andtheunderlyingmechanismbywhichmicroglia identifytheviralparticleleadingtotheproductionofthesecytokinesisunknown. Methodology/Principal Findings: For our studies, we have used murine model of JEV infection as well as BV-2 mouse microgliacellline.Inthisstudy,wehaveidentifiedasignallingpathwaywhichleadstotheactivationofcaspase-1asthekey enzyme responsible for the maturation of both IL-1b and IL-18 in NACHT, LRR and PYD domains-containing protein-3 (NLRP3)dependentmanner.DepletionofNLRP3resultsinthereductionofcaspase-1activityandsubsequentproductionof thesecytokines. Conclusion/Significance: Our results identify a mechanism mediated by Reactive Oxygen Species (ROS) production and potassiumeffluxasthetwodangersignalsthatlinkJEVinfectiontocaspase-1activationresultinginsubsequentIL-1band IL-18maturation. Citation:KaushikDK,GuptaM,KumawatKL,BasuA(2012)NLRP3Inflammasome:KeyMediatorofNeuroinflammationinMurineJapaneseEncephalitis.PLoS ONE7(2):e32270.doi:10.1371/journal.pone.0032270 Editor:TianWang,UniversityofTexasMedicalBranch,UnitedStatesofAmerica ReceivedNovember1,2011;AcceptedJanuary24,2012;PublishedFebruary29,2012 Copyright: ? 2012 Kaushik et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbythecoregrantfromtheDepartmentofBiotechnology,totheNationalBrainResearchCentre,GovernmentofIndia.DKKi