Featured Publications
m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseProgression of NAFLDLineage-restricted deletionFatty liver diseaseMultiple mRNA transcriptsMyeloid cell activationDiet-induced developmentMethyladenosine (m<sup>6</sup>A) RNA modificationMRNA metabolismProtein methyltransferaseLiver diseaseRNA modificationsCellular stressMetabolic reprogrammingDDIT4 mRNACell activationObesityDifferential expressionMammalian targetMRNA transcriptsSignificant downregulationCytokine stimulationPathway activityMetabolic phenotypeMRNA levelsAdenosine 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
2019
Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse
Cai SY, Ge M, Mennone A, Hoque R, Ouyang X, Boyer JL. Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse. Cellular And Molecular Gastroenterology And Hepatology 2019, 9: 679-688. PMID: 31887435, PMCID: PMC7160576, DOI: 10.1016/j.jcmgh.2019.12.008.Peer-Reviewed Original ResearchConceptsWT BDL miceCholestatic liver injuryBDL liversBDL miceBile duct ligationBile acidsLiver injuryCholestatic patientsIL-1βM2 anti-inflammatory macrophagesPrimary sclerosing cholangitisPlasma IL-1βLiver hydroxyproline contentLiver of patientsPrimary biliary cholangitisHealthy control subjectsCD206-positive cellsAnti-inflammatory macrophagesIL-1β inductionEndogenous bile acidsCaspase-1 cleavageProcaspase-1 cleavageMouse hepatocytesSclerosing cholangitisLiver histology
2018
β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway
Chen Y, Ouyang X, Hoque R, Garcia-Martinez I, Yousaf MN, Tonack S, Offermanns S, Dubuquoy L, Louvet A, Mathurin P, Massey V, Schnabl B, Bataller R, Mehal WZ. β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Journal Of Hepatology 2018, 69: 687-696. PMID: 29705237, PMCID: PMC6098974, DOI: 10.1016/j.jhep.2018.04.004.Peer-Reviewed Original ResearchConceptsAlcohol-induced liver injuryAlcoholic hepatitisAlanine aminotransferase levelsLiver injuryNeutrophil influxAminotransferase levelsΒ-hydroxybutyrateDevelopment of AHPlasma alanine aminotransferase levelsGreater neutrophil influxExcess alcohol intakeAlcoholic liver diseaseLife-threatening conditionExcess alcohol consumptionDependent pathwayHigher plasma alanine aminotransferase levelsIntrahepatic macrophagesLiver inflammationLiver diseaseAlcohol intakeHepatoprotective roleReduced steatosisM2 phenotypeTherapeutic effectHepatitis
2016
The SGLT‐2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice
Leng W, Ouyang X, Lei X, Wu M, Chen L, Wu Q, Deng W, Liang Z. The SGLT‐2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice. Mediators Of Inflammation 2016, 2016: 6305735. PMID: 28104929, PMCID: PMC5220517, DOI: 10.1155/2016/6305735.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaApolipoproteins EAtherosclerosisBenzhydryl CompoundsBlood GlucoseBone MarrowDiabetes ComplicationsDiabetes Mellitus, ExperimentalGlucoseGlucosidesInflammasomesInterleukin-18Interleukin-1betaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinReactive Oxygen SpeciesSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsConceptsEffect of dapagliflozinHigh-fat dietIL-1Dapagliflozin treatmentDiabetic atherosclerosisInhibitor dapagliflozinIL-18Reactive oxygen speciesSodium-glucose cotransporter 2 inhibitor dapagliflozinFat metabolismSGLT-2 inhibitor dapagliflozinCaspase-1 pathwayIndices of glucoseHematoxylin-eosin stainingStability of lesionsFormation of atherosclerosisNLRP3 protein levelsOil Red ODiabetic ApoEROS-NLRP3Aortic atherosclerosisMacrophage infiltrationNLRP3 inflammasomeTherapeutic effectMitochondrial reactive oxygen species
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 cellsImmune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis
Morales C, Rachidi S, Hong F, Sun S, Ouyang X, Wallace C, Zhang Y, Garret-Mayer E, Wu J, Liu B, Li Z. Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis. Cancer Research 2014, 74: 446-459. PMID: 24322981, PMCID: PMC4002507, DOI: 10.1158/0008-5472.can-13-1677.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCell Transformation, NeoplasticColitisColonColonic NeoplasmsCrosses, GeneticCytokinesDisease ProgressionDNA RepairGene DeletionGene Expression Regulation, NeoplasticInflammationInterleukin-17Interleukin-23MacrophagesMaleMembrane GlycoproteinsMiceMice, KnockoutMucous MembraneConceptsDNA repair machineryDNA repair pathwaysColon tumorigenesisTumor-associated macrophagesRepair machineryRepair pathwaysOncogenic programEndoplasmic reticulumMutation rateChaperone gp96Β-cateninColon cancerMechanistic underpinningsCellular sitesTumorigenesisReduced expressionEpithelial cellsGenotoxic natureToll-like receptorsInflammation-associated colon cancerImportant driverGp96Inflammation-associated colon tumorigenesisCritical inflammatory cytokinesExpression
2008
Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells
Gu Y, Yang J, Ouyang X, Liu W, Li H, Yang J, Bromberg J, Chen S, Mayer L, Unkeless JC, Xiong H. Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells. European Journal Of Immunology 2008, 38: 1807-1813. PMID: 18506885, PMCID: PMC2733944, DOI: 10.1002/eji.200838331.Peer-Reviewed Original Research