2019
LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes
Huang C, Hedl M, Ranjan K, Abraham C. LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes. Cell Reports 2019, 29: 4525-4539.e4. PMID: 31875558, PMCID: PMC7372507, DOI: 10.1016/j.celrep.2019.11.105.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 6EIF-2 KinaseEndoplasmic ReticulumEndoplasmic Reticulum StressEndoribonucleasesEnterococcus faecalisEscherichia coliGene Expression RegulationHeLa CellsHost-Pathogen InteractionsHumansImmunity, InnateIntracellular Signaling Peptides and ProteinsMacrophagesNod2 Signaling Adaptor ProteinPhagocytosisPrimary Cell CultureProtein Serine-Threonine KinasesRiskSignal TransductionConceptsEndoplasmic reticulumER stressER stress sensorsHuman macrophagesInnate immune outcomesDisease risk variantsMultiple immune-mediated diseasesLaccase domainPattern recognition receptor NOD2HeLa cellsAntimicrobial pathwaysRisk variantsGenetic variantsLACC1Critical roleVariantsMacrophagesATF6IRE1αArg284SignalingReticulumStressTransfectionPERK
2017
Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes
Lahiri A, Hedl M, Yan J, Abraham C. Human LACC1 increases innate receptor-induced responses and a LACC1 disease-risk variant modulates these outcomes. Nature Communications 2017, 8: 15614. PMID: 28593945, PMCID: PMC5472760, DOI: 10.1038/ncomms15614.Peer-Reviewed Original ResearchMeSH KeywordsBacteriaCells, CulturedCrohn DiseaseCytokinesElectron Transport Complex IIExtracellular Signal-Regulated MAP KinasesHumansImmunity, InnateIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMacrophagesNF-kappa BNod2 Signaling Adaptor ProteinP38 Mitogen-Activated Protein KinasesProteinsReactive Oxygen SpeciesReceptors, Pattern RecognitionRNA InterferenceRNA, Small InterferingSuccinate DehydrogenaseConceptsBacterial clearanceCytokine secretionDisease risk variantsReceptor-induced responsesMyeloid-derived cellsNOD2 stimulationRecognition receptorsHuman macrophagesSuccinate dehydrogenaseMtROS productionMitochondrial ROS productionROS productionOutcomesSDH activityMacrophagesSecretionFunctional consequencesClearanceLACC1PRRImportant contributorCellsDisease-associated lociReceptors
2016
IRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation
Hedl M, Yan J, Abraham C. IRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation. Cell Reports 2016, 16: 2442-2455. PMID: 27545875, PMCID: PMC5165654, DOI: 10.1016/j.celrep.2016.07.060.Peer-Reviewed Original ResearchMeSH KeywordsAcetylmuramyl-Alanyl-IsoglutamineAdjuvants, ImmunologicAnimalsCell DifferentiationGene Expression RegulationGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitInterferon Regulatory FactorsInterleukin-1 Receptor-Associated KinasesIntracellular Signaling Peptides and ProteinsMacrophagesMiceMice, Inbred C57BLMice, KnockoutMutationNod2 Signaling Adaptor ProteinPrimary Cell CultureProtein BindingProto-Oncogene Proteins c-aktReceptor-Interacting Protein Serine-Threonine Kinase 2Signal TransductionTNF Receptor-Associated Factor 6ConceptsInterferon regulatory factor 5Akt2 activationPro-inflammatory cytokinesM1 macrophage polarizationGlycolytic pathway genesHuman macrophagesDisease-associated polymorphismsM1 polarizationMacrophage polarizationInflammatory M1 macrophage polarizationPathway genesProximal signalingOligomerization domainRegulatory factor 5Glycolytic pathwayEnhanced glycolysisGenetic variantsGlycolysisMetabolic outcomesIRF5 expressionM1 macrophagesCentral mediatorFactor 5CytokinesMacrophages
2015
Twist1 and Twist2 Contribute to Cytokine Downregulation following Chronic NOD2 Stimulation of Human Macrophages through the Coordinated Regulation of Transcriptional Repressors and Activators
Zheng S, Hedl M, Abraham C. Twist1 and Twist2 Contribute to Cytokine Downregulation following Chronic NOD2 Stimulation of Human Macrophages through the Coordinated Regulation of Transcriptional Repressors and Activators. The Journal Of Immunology 2015, 195: 217-226. PMID: 26019273, PMCID: PMC4501480, DOI: 10.4049/jimmunol.1402808.Peer-Reviewed Original ResearchMeSH KeywordsAcetylmuramyl-Alanyl-IsoglutamineActivating Transcription Factor 4Antibodies, NeutralizingCCAAT-Enhancer-Binding ProteinsCore Binding Factor Alpha 1 SubunitCore Binding Factor Alpha 2 SubunitGene Expression RegulationHumansInterleukin-10Macrophage ActivationMacrophagesNod2 Signaling Adaptor ProteinNuclear ProteinsPolycomb Repressive Complex 1Primary Cell CulturePromoter Regions, GeneticProtein BindingProto-Oncogene Proteins c-mafRepressor ProteinsRNA, Small InterferingSignal TransductionTranscription, GeneticTransforming Growth Factor betaTwist-Related Protein 1ConceptsChronic NOD2 stimulationCytokine downregulationNOD2 stimulationTwist2 expressionHuman macrophagesTGF-β dependentIntestinal immune homeostasisC-MafOligomerization domain 2IL-10Intestinal macrophagesImmune homeostasisTranscription factor 4PRR stimulationAcute stimulationDecreased expressionMacrophagesBMI1 expressionCytokinesNOD2StimulationTwist1DownregulationTranscriptional repressor Bmi1Factor 4
2014
A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8–induced IL-1
Hedl M, Abraham C. A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8–induced IL-1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 13451-13456. PMID: 25197060, PMCID: PMC4169936, DOI: 10.1073/pnas.1404178111.Peer-Reviewed Original ResearchMeSH KeywordsAcetylmuramyl-Alanyl-IsoglutamineADAM ProteinsADAM17 ProteinCaspase 8Cells, CulturedGenetic Predisposition to DiseaseHumansInterleukin-1LigandsMacrophagesMitogen-Activated Protein KinasesMycobacteriumMyeloid CellsNF-kappa BNod2 Signaling Adaptor ProteinPhosphatidylinositol 3-KinasesPolymorphism, Single NucleotideReceptors, Pattern RecognitionReceptors, Tumor Necrosis Factor, Member 25Signal TransductionSolubilityTissue Inhibitor of Metalloproteinase-3Tumor Necrosis Factor Ligand Superfamily Member 15ConceptsMost risk lociCaspase-8-dependent pathwayCytokine secretionGain of functionIntestinal myeloid cellsInflammatory bowel diseaseRisk lociIL-1 secretionTNFSF15 expressionPI3KPRR responsesBowel diseaseSignalingCytokine productionImmune homeostasisInflammatory diseasesHuman macrophagesIL-1Myeloid cellsAltered functionCytokinesTNFSF15MacrophagesSecretionDisease
2013
NF-κB1 Inhibits NOD2-Induced Cytokine Secretion through ATF3-Dependent Mechanisms
Zheng S, Abraham C. NF-κB1 Inhibits NOD2-Induced Cytokine Secretion through ATF3-Dependent Mechanisms. Molecular And Cellular Biology 2013, 33: 4857-4871. PMID: 24100018, PMCID: PMC3889551, DOI: 10.1128/mcb.00797-13.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 3AnimalsCells, CulturedCytokinesEpigenesis, GeneticGene Knockdown TechniquesHistonesHumansIleumMacrophagesMiceMice, Inbred C57BLMice, KnockoutNF-kappa B p50 SubunitNod1 Signaling Adaptor ProteinNod2 Signaling Adaptor ProteinPrimary Cell CulturePromoter Regions, GeneticProtein Processing, Post-TranslationalToll-Like Receptor 2Toll-Like Receptor 4Transcriptional ActivationConceptsChronic NOD2 stimulationIntestinal immune homeostasisCytokine secretionNOD2 stimulationNF-κB1Immune homeostasisHuman macrophagesNF-κB pathwayNF-κB1 expressionCytokine downregulationInhibitory pathwaysNOD2ATF3 expressionSecretionIntestinal environmentGene promoterCytokine gene promotersStimulationInhibitory histone modificationsATF3MacrophagesKnockdown conditionsCritical mechanismHomeostasisCytokines