2022
MIF is a common genetic determinant of COVID-19 symptomatic infection and severity
Shin JJ, Fan W, Par-Young J, Piecychna M, Leng L, Israni-Winger K, Qing H, Gu J, Zhao H, Schulz WL, Unlu S, Kuster J, Young G, Liu J, Ko AI, Garcia A, Sauler M, Wisnewski AV, Young L, Orduña A, Wang A, Klementina O, Garcia AB, Hegyi P, Armstrong ME, Mitchell P, Ordiz DB, Garami A, Kang I, Bucala R. MIF is a common genetic determinant of COVID-19 symptomatic infection and severity. QJM 2022, 116: 205-212. PMID: 36222594, PMCID: PMC9620729, DOI: 10.1093/qjmed/hcac234.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLow-expression MIF alleleCOVID-19 infectionMIF allelesCATT7 alleleHealthy controlsCOVID-19Serum macrophage migration inhibitory factorSymptomatic SARS-CoV-2 infectionHigher serum MIF levelsHigh-expression MIF allelesRetrospective case-control studySARS-CoV-2 infectionFunctional polymorphismsAvailable clinical characteristicsMultinational retrospective studySerum MIF levelsUninfected healthy controlsSymptomatic COVID-19Tertiary medical centerHealthy control subjectsCase-control studyMigration inhibitory factorCoronavirus disease 2019Common functional polymorphisms
2019
Cardiomyocyte d-dopachrome tautomerase protects against heart failure
Ma Y, Su KN, Pfau D, Rao VS, Wu X, Hu X, Leng L, Du X, Piecychna M, Bedi K, Campbell SG, Eichmann A, Testani JM, Margulies KB, Bucala R, Young LH. Cardiomyocyte d-dopachrome tautomerase protects against heart failure. JCI Insight 2019, 4: e128900. PMID: 31484822, PMCID: PMC6777911, DOI: 10.1172/jci.insight.128900.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCardiomegalyCytokinesDisease Models, AnimalEchocardiographyGene DeletionGene ExpressionGenetic Predisposition to DiseaseHeart FailureHumansIntramolecular OxidoreductasesMaleMAP Kinase Kinase KinasesMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacRecombinant ProteinsSignal TransductionTranscriptomeVascular Endothelial Growth Factor AConceptsTransverse aortic constrictionHeart failureRecombinant DDTConnective tissue growth factor expressionTissue growth factor expressionMore interstitial fibrosisAdvanced heart failureCardiac pressure overloadExperimental heart failureCardiac contractile dysfunctionLittermate control miceSmad-2 activationGrowth factor expressionSarcoplasmic reticulum calcium ATPaseMacrophage migration inhibitory factor (MIF) familyReticulum calcium ATPasePulmonary edemaCardiac dilatationContractile dysfunctionControl miceInterstitial fibrosisPressure overloadAntifibrotic actionAortic constrictionLow VEGF
2018
Macrophage migration inhibitory factor mediates metabolic dysfunction induced by atypical antipsychotic therapy
Cui D, Peng Y, Zhang C, Li Z, Su Y, Qi Y, Xing M, Li J, Kim GE, Su KN, Xu J, Wang M, Ding W, Piecychna M, Leng L, Hirasawa M, Jiang K, Young L, Xu Y, Qi D, Bucala R. Macrophage migration inhibitory factor mediates metabolic dysfunction induced by atypical antipsychotic therapy. Journal Of Clinical Investigation 2018, 128: 4997-5007. PMID: 30295645, PMCID: PMC6205380, DOI: 10.1172/jci93090.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorAtypical antipsychotic therapyMIF expressionMigration inhibitory factorInsulin resistanceAntipsychotic therapyAtypical antipsychoticsMetabolic dysfunctionOlanzapine-induced insulin resistanceInhibitory factorDrug-naive schizophrenic patientsMetabolic side effectsPlasma lipid concentrationsAbnormal fat depositionAdverse metabolic sequelaeMIF concentrationsOlanzapine monotherapyMetabolic sequelaeOlanzapine administrationIntracerebroventricular injectionMIF antibodyFood intakeClinical utilitySchizophrenic patientsSide effects
2017
MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics
Tilstam PV, Qi D, Leng L, Young L, Bucala R. MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics. Expert Opinion On Therapeutic Targets 2017, 21: 671-683. PMID: 28562118, PMCID: PMC6130320, DOI: 10.1080/14728222.2017.1336227.BooksConceptsMacrophage migration inhibitory factorMIF family membersCardiovascular diseaseFamily cytokinesTherapeutic opportunitiesIschemia-reperfusion injuryChemokine-like functionsMigration inhibitory factorNovel therapeutic opportunitiesPro-survival mediatorsFamily membersInflammatory pathogenesisMyocardial infarctionMyocardial ischemiaClinical studiesPleiotropic cytokineImmune systemInhibitory factorReceptor pathwayCytokinesDiseaseMIF-2Active investigationMIF familyClinical translation
2014
The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury
Qi D, Atsina K, Qu L, Hu X, Wu X, Xu B, Piecychna M, Leng L, Fingerle-Rowson G, Zhang J, Bucala R, Young LH. The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury. Journal Of Clinical Investigation 2014, 124: 3540-3550. PMID: 24983315, PMCID: PMC4109524, DOI: 10.1172/jci73061.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorContractile dysfunctionAntibody-dependent neutralizationAutocrine/paracrine effectsCoronary artery ligationCardiac contractile dysfunctionMigration inhibitory factorLV contractile dysfunctionDopachrome tautomeraseMolecular signaling pathwaysArtery ligationIschemic injuryCardiac sizeCardiomyocyte secretionControl heartsProtective effectKnockout miceParacrine effectsIschemic stressPhysiologic responsesInhibitory factorMore necrosisDysfunctionInjuryMurine cardiomyocytes
2013
Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction
Wang J, Tong C, Yan X, Yeung E, Gandavadi S, Hare AA, Du X, Chen Y, Xiong H, Ma C, Leng L, Young LH, Jorgensen WL, Li J, Bucala R. Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction. Circulation 2013, 128: 225-236. PMID: 23753877, PMCID: PMC3781594, DOI: 10.1161/circulationaha.112.000862.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCardiotonic AgentsCells, CulturedGlucoseHistocompatibility Antigens Class IIIntramolecular OxidoreductasesIsoxazolesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLMice, KnockoutMyocardial InfarctionMyocardial IschemiaMyocytes, CardiacRecombinant ProteinsSignal TransductionConceptsMacrophage migration inhibitory factorCardiac ischemic injuryIschemic injuryProtective effectPostischemic left ventricular functionGlucose uptakeLeft coronary artery occlusionLeft ventricular functionCoronary artery occlusionIschemic tissue injuryMigration inhibitory factorMyocardial glucose uptakeAMPK activationTreatment of cardiomyocytesArtery occlusionMIF receptorVentricular functionIschemic myocardiumCellular glucose uptakeTissue injuryIschemia modelPharmacological augmentationFlow ischemiaSuch agonistsInhibitory factor
2009
Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion
Qi D, Hu X, Wu X, Merk M, Leng L, Bucala R, Young LH. Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. Journal Of Clinical Investigation 2009, 119: 3807-3816. PMID: 19920350, PMCID: PMC2786800, DOI: 10.1172/jci39738.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineEnzyme ActivationHumansIn Vitro TechniquesIntramolecular OxidoreductasesJNK Mitogen-Activated Protein KinasesMacrophage Migration-Inhibitory FactorsMAP Kinase Kinase 4MiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMyocardial ContractionMyocardial Reperfusion InjuryMyocardiumReceptors, ImmunologicSignal TransductionConceptsMacrophage migration inhibitory factorIschemia/reperfusionMIF deficiencyCardiac injuryMIF allelesJNK pathway activationRole of MIFRecombinant macrophage migration inhibitory factorExperimental ischemia/reperfusionLow-expression MIF allelePathway activationGreater contractile dysfunctionMIF-/- miceMigration inhibitory factorJNK activationReperfusion injuryContractile dysfunctionCoronary occlusionProinflammatory cytokinesWT heartsReperfusionCell death (BAD) phosphorylationInjuryClinical implicationsInhibitory factor