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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Role for NOD2 in Mycobacterium tuberculosis‐induced iNOS expression and NO production in human macrophages
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Role for NOD2 in Mycobacterium tuberculosis‐induced iNOS expression and NO production in human macrophages

机译:NOD2在结核分枝杆菌诱导的人巨噬细胞中iNOS表达和NO产生中的作用

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摘要

M.tb,whichcausesTB,isahost‐adaptedintracellularpathogenofmacrophages.MacrophageintracellularPRRs,suchasNODproteins,regulateproinflammatorycytokineproductioninresponsetovariouspathogenicorganisms.WedemonstratedpreviouslythatNOD2playsanimportantroleincontrollingtheinflammatoryresponseandviabilityofM.tbandMycobacteriumbovisBCGinhumanmacrophages.Variousinflammatorymediators,suchascytokines,ROS,andRNS,suchasNO,canmediatethiscontrol.iNOS(orNOS2)isakeyenzymeforNOproductionandM.tbcontrolduringinfectionofmousemacrophages;however,theroleofNOduringinfectionofhumanmacrophagesremainsunclear,inpart,asaresultofthelowamountsofNOproducedinthesecells.Here,wetestedthehypothesisthatactivationofNOD2byitsligands(MDPandGMDP,thelatterfromM.tb)playsanimportantroleintheexpressionandactivityofiNOSandNOproductioninhumanmacrophages.WedemonstratethatM.tborM.bovisBCGinfectionenhancesiNOSexpressioninhumanmacrophages.TheM.tb‐inducediNOSexpressionandNOproductionaredependentonNOD2expressionduringM.tbinfection.Finally,NF‐κBactivationisrequiredforNOD2‐dependentexpressionofiNOSinhumanmacrophages.OurdataprovideevidenceforanewmolecularpathwaythatlinksactivationofNOD2,animportantintracellularPRR,andiNOSexpressionandactivityduringM.tbinfectionofhumanmacrophages...
机译:结核分枝杆菌,whichcausesTB,isahost-adaptedintracellularpathogenofmacrophages.MacrophageintracellularPRRs,suchasNODproteins,regulateproinflammatorycytokineproductioninresponsetovariouspathogenicorganisms.WedemonstratedpreviouslythatNOD2playsanimportantroleincontrollingtheinflammatoryresponseandviabilityofM.tbandMycobacteriumbovisBCGinhumanmacrophages.Variousinflammatorymediators,suchascytokines,ROS,andRNS,suchasNO,canmediatethiscontrol.iNOS(orNOS2)isakeyenzymeforNOproductionandM.tbcontrolduringinfectionofmousemacrophages;然而,theroleofNOduringinfectionofhumanmacrophagesremainsunclear,inpart,asaresultofthelowamountsofNOproducedinthesecells.Here,我们测试了一个假设,即配体(MDP和GMDP,来自M.tb的激活)对NOD2的激活在人类巨噬细胞中iNOS和NO的表达和活性中起着重要的作用。我们证明了M.tborM.bovis BC感染感染增强了NO的表达,而在人类巨噬细胞中没有表达NF。 iNOS在人类巨噬细胞中依赖NOD2的表达需要κB激活。我们的数据提供了一种新的分子途径的证据,该途径将NOD2的激活,重要的细胞内PRR和iNOS的表达与活性联系起来。

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