Featured Publications
GSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activation
Arumugam S, Qin Y, Liang Z, Han SN, Boodapati SLT, Li J, Lu Q, Flavell RA, Mehal WZ, Ouyang X. GSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activation. Cell Death & Differentiation 2022, 29: 2060-2069. PMID: 35477991, PMCID: PMC9525599, DOI: 10.1038/s41418-022-00997-y.Peer-Reviewed Original ResearchConceptsInflammasome assemblyGlycogen synthase kinase-3βSynthase kinase-3βOrganelle dynamicsGolgi networkSubcellular machineryGolgi apparatusInflammasome activationMechanistic basisKinase-3βMolecular determinantsSpatiotemporal dynamicsGSK3β activationMitochondriaNLRP3 oligomerizationTGNSubsequent bindingGSK3βNLRP3 inflammasome activationActivationNew avenuesAssemblyStepwise processOrganellesPhosphatidylinositolThe DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury
Hu B, Jin C, Li HB, Tong J, Ouyang X, Cetinbas NM, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Yilmaz O, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 2016, 354: 765-768. PMID: 27846608, PMCID: PMC5640175, DOI: 10.1126/science.aaf7532.Peer-Reviewed Original ResearchConceptsCell deathDNA sensor AIM2New therapeutic targetsCaspase-1-dependent deathIntestinal epithelial cellsBone marrow cellsGastrointestinal syndromeTissue injuryInflammasome activationGastrointestinal tractRadiation-induced cell deathRadiation-induced DNA damageTherapeutic targetAcute exposureBone marrowChemotherapeutic agentsMarrow cellsRadiation exposureAIM2Massive cell deathEpithelial cellsHematopoietic failureDeathMolecular mechanismsDNA damageAdenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway
Ouyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ. Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway. Nature Communications 2013, 4: 2909. PMID: 24352507, PMCID: PMC3895487, DOI: 10.1038/ncomms3909.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine TriphosphateAnimalsCarrier ProteinsCyclic AMPCyclic AMP Response Element-Binding ProteinCyclic AMP-Dependent Protein KinasesHypoxia-Inducible Factor 1, alpha SubunitInflammasomesInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Adenosine A2ASignal TransductionConceptsHIF-1α pathwayInflammasome activityInflammasome activationA2A receptorsIL-1β productionIL-1β responseReceptor-mediated signalingLack of responseTolerogenic stateChronic diseasesInflammatory responseInflammasome pathwayPrevious exposureLipopolysaccharideAdenosineReceptorsActivationKey regulatorInitial activationPathwaySignalingResponseInterleukinStimuliDisease
2020
Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction
Wang S, Su X, Xu L, Chang C, Yao Y, Komal S, Cha X, Zang M, Ouyang X, Zhang L, Han S. Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction. Journal Of Molecular And Cellular Cardiology 2020, 149: 82-94. PMID: 32991876, DOI: 10.1016/j.yjmcc.2020.09.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCARD Signaling Adaptor ProteinsEnzyme ActivationFibroblastsGlycogen Synthase Kinase 3 betaIndolesInflammasomesInflammationMaleMaleimidesMyocardial InfarctionMyocardial IschemiaMyocytes, CardiacNLR Family, Pyrin Domain-Containing 3 ProteinProtein Kinase InhibitorsProtein MultimerizationRats, Sprague-DawleyVascular RemodelingConceptsNLRP3 inflammasome activationGSK-3β inhibitionMyocardial infarctionInflammasome activationNOD-like receptor family pyrin domainGSK-3βFamily pyrin domainGlycogen synthase kinase-3β inhibitionCardiac dysfunctionMyocardial dysfunctionCardiac damageHeart dysfunctionHeart diseaseSterile inflammationInflammatory responseRat modelDay 2Pyrin domainCardiac fibroblastsSuccessful inductionHypoxia treatmentDysfunctionGSK-3 activityHuman cardiomyocytesInflammasome stimulation
2014
Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway
Farooq A, Hoque R, Ouyang X, Farooq A, Ghani A, Ahsan K, Guerra M, Mehal WZ. Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway. AJP Gastrointestinal And Liver Physiology 2014, 307: g732-g740. PMID: 25104498, PMCID: PMC4187065, DOI: 10.1152/ajpgi.00073.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsAspartic AcidBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCaspase 1Cell LineChemical and Drug Induced Liver InjuryDisease Models, AnimalExcitatory Amino Acid AgonistsHumansInflammasomesInterleukin-1betaLiverMacrophagesMaleMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinPancreatitisProtein PrecursorsReceptors, N-Methyl-D-AspartateSignal TransductionTime FactorsConceptsNMDA receptorsAcute hepatitisLiver inflammationInflammasome activityAcute inflammatory liver injuryNOD-like receptor familyN-methyl-D-aspartate (NMDA) receptor familyChronic liver inflammationInflammatory liver injuryΒ-arrestinBrain NMDA receptorsReceptor familyNMDA receptor pathwayLigand-gated ion channelsLiver injuryNonalcoholic steatohepatitisImmune suppressionLimits injuryNF-kβImmune regulationInflammasome activationKupffer cellsInflammasome machineryPyrin domainNonneuronal cells