2024
Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma
Valdez C, Sánchez-Zuno G, Osmani L, Ibrahim W, Galan A, Bacchiocchi A, Halaban R, Kulkarni R, Kang I, Bucala R, Tran T. Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma. Oncotarget 2024, 15: 507-520. PMID: 39028303, PMCID: PMC11259151, DOI: 10.18632/oncotarget.28615.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, Differentiation, B-LymphocyteBiomarkers, TumorFemaleHistocompatibility Antigens Class IIHumansImmune Checkpoint InhibitorsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMelanomaMiddle AgedMutationPrognosisRetrospective StudiesSkin NeoplasmsConceptsMacrophage migration inhibitory factorImmune checkpoint inhibitionD-dopachrome tautomeraseExpression of macrophage migration inhibitory factorDrivers of tumor progressionInflammatory cell markersPatient tumor samplesPatient survival outcomesMigration inhibitory factorStatistically significant differenceCheckpoint inhibitionImmune therapyPrognostic valueSurvival outcomesResistant melanomaGene expressionImproved survivalRetrospective studyInflammatory markersTumor progressionCell markersTumor samplesClinical evidenceMelanomaBulk RNA sequencingMIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study
Ye S, Agalave N, Ma F, Mahmood D, Al-Grety A, Khoonsari P, Leng L, Svensson C, Bucala R, Kultima K, Vera P. MIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study. International Journal Of Molecular Sciences 2024, 25: 4484. PMID: 38674069, PMCID: PMC11050327, DOI: 10.3390/ijms25084484.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteCystitis, InterstitialDisease Models, AnimalFemaleHistocompatibility Antigens Class IIHyperalgesiaIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMiceProteomicsReceptors, CXCR4Receptors, ImmunologicSpinal CordUrinary BladderConceptsMacrophage migration inhibitory factorProtease activated receptor 4C-X-C chemokine receptor type 4Bladder hyperalgesiaBladder painSpinal proteinsMIF receptor CD74MIF antagonismL6-S1 spinal segmentsSpinal mechanismsInterstitial cystitis/bladder pain syndromeMIF receptorSeparate groups of miceChemokine receptor type 4Associated with reliefGroups of miceC-X-CMigration inhibitory factorChanges compared to controlsBladder inflammationPain syndromeFemale miceNo significant changesSham i.Receptor 4
2022
CD74 as a regulator of transcription in normal B cells
David K, Friedlander G, Pellegrino B, Radomir L, Lewinsky H, Leng L, Bucala R, Becker-Herman S, Shachar I. CD74 as a regulator of transcription in normal B cells. Cell Reports 2022, 41: 111572. PMID: 36323260, DOI: 10.1016/j.celrep.2022.111572.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesHistocompatibility Antigens Class IIHumansLeukemia, Lymphocytic, Chronic, B-CellProtein BindingSignal TransductionTranscription FactorsTranscription, GeneticConceptsMacrophage migration inhibitory factorNormal B cellsB cellsCytokine macrophage migration inhibitory factorRegulators of transcriptionChronic lymphocytic leukemia cellsMigration inhibitory factorNovel therapeutic pathwaysInhibition of transcriptionLymphocytic leukemia cellsTumor suppressor geneTranscriptional regulatorsTranscription factorsTherapeutic pathwaysCLL cellsFuture treatmentIntracellular domainOncogenic transformationMalignant cellsInhibitory factorRegulatory functionsPromoter areaLeukemia cellsTranscriptionGenes“Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct
Vandenbark AA, Meza-Romero R, Wiedrick J, Gerstner G, Seifert H, Kent G, Piechycna M, Benedek G, Bucala R, Offner H. “Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct. Cellular Immunology 2022, 378: 104561. PMID: 35738135, PMCID: PMC9714992, DOI: 10.1016/j.cellimm.2022.104561.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAcute experimental autoimmune encephalomyelitisDRα1-MOG-35Multiple sclerosisMIF-1EAE scoresMale miceMIF-2Severe diseaseMacrophage migration inhibitory factorClinical EAE scoresMIF-deficient micePeripheral inflammatory cellsMigration inhibitory factorSpinal cord tissueT cell activationSex-dependent differencesEAE severityAutoimmune encephalomyelitisSerum levelsTreatment of WTInflammatory cellsFemale miceClinical signsCord tissueCD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis
Chen L, Yin Z, Qin X, Zhu X, Chen X, Ding G, Sun D, Wu NN, Fei J, Bi Y, Zhang J, Bucala R, Ren J, Zheng Q. CD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis. Pharmacological Research 2022, 176: 106086. PMID: 35033649, DOI: 10.1016/j.phrs.2022.106086.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntigens, Differentiation, B-LymphocyteCell LineDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2FemaleFerroptosisGene ExpressionHistocompatibility Antigens Class IIHumansMacrophage Migration-Inhibitory FactorsMaleMice, KnockoutMiddle AgedMyocardial ContractionMyocardiumNLR Family, Pyrin Domain-Containing 3 ProteinOxidative StressOxygen ConsumptionPyroptosisRatsVentricular RemodelingConceptsHigh glucose/high fatMacrophage migration inhibitory factorCardiac remodelingContractile dysfunctionCell death domainGene Ontology termsInhibitors of MIFRecombinant macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorType 2 diabetes mellitusOntology termsDeath domainLipid peroxidationGlobal metabolic defectsKEGG analysisPlasma MIF levelsInjection of streptozotocinMitochondrial defectsHigh-fat dietMigration inhibitory factorInhibitor of NLRP3Cell deathPrecise interplayMitochondrial dysfunctionCognate receptors
2021
Macrophage migration inhibitory factor exerts pro‐proliferative and anti‐apoptotic effects via CD74 in murine hepatocellular carcinoma
Wirtz TH, Saal A, Bergmann I, Fischer P, Heinrichs D, Brandt EF, Koenen MT, Djudjaj S, Schneider KM, Boor P, Bucala R, Weiskirchen R, Bernhagen J, Trautwein C, Berres M. Macrophage migration inhibitory factor exerts pro‐proliferative and anti‐apoptotic effects via CD74 in murine hepatocellular carcinoma. British Journal Of Pharmacology 2021, 178: 4452-4467. PMID: 34250589, DOI: 10.1111/bph.15622.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteApoptosisCarcinoma, HepatocellularHistocompatibility Antigens Class IILiver NeoplasmsMacrophage Migration-Inhibitory FactorsMiceSignal TransductionConceptsMacrophage migration inhibitory factorMIF/CD74 axisMigration inhibitory factorHepatocellular carcinomaRole of MIFInhibitory factorReduced tumor burdenAnti-CD74 antibodiesNew pharmacological therapiesDEN/CClDifferent inflammatory diseasesChemokine-like proteinTherapy-induced cell deathMurine hepatocellular carcinomaPro-tumorigenic roleAnti-apoptotic effectsCarbon tetrachloride modelTherapy-induced apoptosisMIF knockoutMIF receptorPharmacological therapyTumor burdenControl miceReceptor CD74CD74 antibodyIntravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain
Ye S, Ma F, Mahmood DFD, Meyer-Siegler KL, Menard RE, Hunt DE, Leng L, Bucala R, Vera PL. Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain. PLOS ONE 2021, 16: e0255975. PMID: 34424927, PMCID: PMC8382170, DOI: 10.1371/journal.pone.0255975.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorHigh mobility group box 1Bladder painMIF receptorHMGB1 releaseBladder hyperalgesiaMobility group box 1MIF receptor CD74Migration inhibitory factorGroup box 1Primary urothelial cellsInhibitory factor receptorWarrants further investigationCD74 receptorReceptor CD74Micturition parametersReceptor antagonistReceptor 4Box 1PainInhibitory factorHyperalgesiaCD74Urothelial cellsNovel targetCD74 is a regulator of hematopoietic stem cell maintenance
Becker-Herman S, Rozenberg M, Hillel-Karniel C, Gil-Yarom N, Kramer M, Barak A, Sever L, David K, Radomir L, Lewinsky H, Levi M, Friedlander G, Bucala R, Peled A, Shachar I. CD74 is a regulator of hematopoietic stem cell maintenance. PLOS Biology 2021, 19: e3001121. PMID: 33661886, PMCID: PMC7963458, DOI: 10.1371/journal.pbio.3001121.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntigens, Differentiation, B-LymphocyteBone Marrow CellsBone Marrow TransplantationCell LineageFemaleHealthy VolunteersHematopoietic Stem CellsHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLSignal TransductionConceptsMacrophage migration inhibitory factorHematopoietic stem cellsBone marrowCytokine macrophage migration inhibitory factorMigration inhibitory factorNumber of HSPCsTransplant protocolsCD18 expressionClinical transplantationInduced SurvivalCD74Inhibitory factorBM nicheCell surface receptorsSelf-renewal propertiesClinical insightsProgenitor cellsBlood cell lineagesSurface receptorsStem cellsHematopoietic stemCell lineagesCellsUndifferentiated cellsHematopoietic stem cell maintenanceHsp90-stabilized MIF supports tumor progression via macrophage recruitment and angiogenesis in colorectal cancer
Klemke L, De Oliveira T, Witt D, Winkler N, Bohnenberger H, Bucala R, Conradi LC, Schulz-Heddergott R. Hsp90-stabilized MIF supports tumor progression via macrophage recruitment and angiogenesis in colorectal cancer. Cell Death & Disease 2021, 12: 155. PMID: 33542244, PMCID: PMC7862487, DOI: 10.1038/s41419-021-03426-z.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenic ProteinsAnimalsAntigens, Differentiation, B-LymphocyteAntineoplastic AgentsColitis-Associated NeoplasmsDisease Models, AnimalFemaleHCT116 CellsHEK293 CellsHistocompatibility Antigens Class IIHSP90 Heat-Shock ProteinsHumansInflammation MediatorsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMice, Inbred C57BLMice, KnockoutNeovascularization, PathologicOrganoidsProtein StabilitySignal TransductionTumor BurdenTumor-Associated MacrophagesConceptsMacrophage migration inhibitory factorMIF levelsMacrophage recruitmentAction of MIFColitis-associated colorectal cancer (CAC) mouse modelTumor growthTumor progressionFunction of MIFColorectal cancer mouse modelHigher MIF levelsHost inflammatory pathwaysTumor-specific functionsEpithelial cellsShorter overall survivalCRC tumor progressionClinical correlation studiesMigration inhibitory factorCRC tumor growthCancer mouse modelWild-type organoidsTumor epithelial cellsHSP90 inhibitor treatmentCD74 expressionOverall survivalCRC patients