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 processOrganellesPhosphatidylinositolDigoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 339-350.e3. PMID: 29414684, PMCID: PMC5806149, DOI: 10.1016/j.cmet.2018.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell NucleusChromatinDigoxinDisease Models, AnimalEndotoxinsHistonesHumansHypoxia-Inducible Factor 1, alpha SubunitInflammationLiverNon-alcoholic Fatty Liver DiseaseOxidation-ReductionProtein BindingPyruvate KinaseTHP-1 CellsTranscription, GeneticTranscriptional ActivationConceptsHIF-1α transactivationSterile inflammationHIF-1α pathway activationNon-alcoholic steatohepatitisKinase M2Major clinical consequencesAbility of digoxinLiver inflammationLiver diseasePyruvate kinase M2Clinical consequencesTherapeutic targetInflammationTissue damageHIF-1αPathway activationDigoxinOxidative stressCardiac glycosidesSteatohepatitisDigoxin bindsNovel roleLiverUbiquitous responseActivationAdenosine 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
2016
Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9
Garcia-Martinez I, Santoro N, Chen Y, Hoque R, Ouyang X, Caprio S, Shlomchik MJ, Coffman RL, Candia A, Mehal WZ. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. Journal Of Clinical Investigation 2016, 126: 859-864. PMID: 26808498, PMCID: PMC4767345, DOI: 10.1172/jci83885.Peer-Reviewed Original ResearchConceptsDevelopment of NASHNonalcoholic steatohepatitisTLR9 pathwayTLR9 pathway activationCommon liver diseaseObesity-induced changesHigh-fat dietActivation of TLR9Progressive diseaseLiver diseaseInflammatory phenotypeTLR9 antagonistTLR9Animal modelsPlasma mtDNAHepatocyte originPathway activationSteatohepatitisDiseaseMiceCellular requirementsActivationActivation capacityHigh levelsCirrhosis
2007
Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation
Ouyang X, Negishi H, Takeda R, Fujita Y, Taniguchi T, Honda K. Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. Biochemical And Biophysical Research Communications 2007, 354: 1045-1051. PMID: 17275788, DOI: 10.1016/j.bbrc.2007.01.090.Peer-Reviewed Original ResearchConceptsToll-like receptorsInterferon regulatory factor 5TLR synergyTRIF pathwayImmune systemMultiple Toll-like receptorsTranscription factor interferon regulatory factor 5Regulatory factor 5Agonist combinationsImmune cellsMyD88 adaptorInnate immunityIRF5 activationTRIF adaptorMyD88Synergistic inductionActivationFactor 5Target genesCross talkCellsAgonistsTRIFPathwayImmunity