2024
Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissueA small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus
Li J, Leng L, Pantouris G, Manjula R, Piecychna M, Abriola L, Hu B, Lolis E, Armstrong M, Donnelly S, Bucala R. A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus. Journal Of Biological Chemistry 2024, 300: 107443. PMID: 38838773, PMCID: PMC11259703, DOI: 10.1016/j.jbc.2024.107443.Peer-Reviewed Original ResearchPromoter microsatellitesGene expressionMicrosatellite repeat numberMacrophage migration inhibitory factorLength-dependent mannerRNA expression analysisSusceptibility lociFunctional variantsSmall molecule inhibitorsExpression analysisPharmacogenomic developmentRepeat numberMicrosatelliteFunctional interactionsTranscription inhibitorInflammatory gene expressionMIF mRNA expressionCytokine macrophage migration inhibitory factorTranscriptionGenesProtein expressionMigration inhibitory factorExpressionInhibitory factorExpressing macrophagesMacrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis
Yang H, Li J, Huang X, Bucala R, Xu A, Lan H. Macrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis. Frontiers In Immunology 2024, 15: 1361343. PMID: 38846956, PMCID: PMC11153660, DOI: 10.3389/fimmu.2024.1361343.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorMigration inhibitory factorTreatment of immune-mediated kidney diseasesMacrophage MIFMIF depletionPathogenic roleSource of MIFImmune-mediated kidney diseasesAnti-glomerular basement membrane glomerulonephritisInhibitory factorT cell recruitmentGlomerular crescent formationTh17 immune responsesReduced serum creatininePolarization of macrophagesRenal macrophagesSerum creatinineCrescentic glomerulonephritisInhibiting Th1Renal injuryControl miceCreatine clearanceCrescent formationMembranous glomerulonephritisConditional ablationMIF contribution to progressive brain diseases
Matejuk A, Benedek G, Bucala R, Matejuk S, Offner H, Vandenbark A. MIF contribution to progressive brain diseases. Journal Of Neuroinflammation 2024, 21: 8. PMID: 38178143, PMCID: PMC10765708, DOI: 10.1186/s12974-023-02993-6.Peer-Reviewed Original ResearchConceptsBrain diseasesMultiple sclerosisAlzheimer's diseaseMacrophage migration inhibitory factorModulation of neuroinflammationNumerous neurologic diseasesMigration inhibitory factorProgressive brain diseaseNew therapeutic strategiesInflammatory mediatorsChronic inflammationAutoimmune diseasesVascular diseaseNervous system developmentNeurologic diseaseNeuroendocrine functionPsychiatric disordersTherapeutic strategiesEconomic burdenNeurological diseasesNew biomarkersInhibitory factorNeurodegenerative pathologiesDiseaseNovel therapeuticsMacrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review
Jarmula J, Lee J, Lauko A, Rajappa P, Grabowski M, Dhawan A, Chen P, Bucala R, Vogelbaum M, Lathia J. Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review. Neuro-Oncology Advances 2024, 6: vdae142. PMID: 39233830, PMCID: PMC11372298, DOI: 10.1093/noajnl/vdae142.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorPrimary CNS tumorsCentral nervous systemMigration inhibitory factorCNS tumorsPrimary central nervous systemInhibitory factorTherapeutic targetPre-clinical studiesFunctions of macrophage migration inhibitory factorPreclinical modelsImmune evasionSmall molecule inhibitorsNeuro-oncologyClinical trialsTumor initiationClinical translationMonoclonal antibodiesTumorigenic processNervous systemTherapeutic requirementsCell proliferationTherapeutic developmentTumorEffective target
2023
Extracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity
Chen L, Li L, Cui D, Huang Y, Tong H, Zabihi H, Wang S, Qi Y, Lakowski T, Leng L, Liu S, Wu H, Young L, Bucala R, Qi D. Extracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity. Molecular Metabolism 2023, 79: 101834. PMID: 37935315, PMCID: PMC10700858, DOI: 10.1016/j.molmet.2023.101834.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorExtracellular MIFHigh-fat dietHormone-sensitive lipaseDevelopment of obesityMigration inhibitory factorInhibitory factorRole of cytokinesExtracellular actionJNK phosphorylationMIF levelsSevere obesityHFD miceHFD feedingMIF antibodyWT miceAdipocyte hypertrophyCOP9 signalosome subunit 5Fat dietHSL expressionObesityAutocrine fashionHSL activationSensitive lipaseInhibitory action830 Inhibition of macrophage migration inhibitory factor (MIF) to overcome immune checkpoint resistance in melanoma
Sanchez-Zuno G, Caulfield J, Leng L, Zhang L, Jilaveanu L, Kluger H, Bucala R, Tran T. 830 Inhibition of macrophage migration inhibitory factor (MIF) to overcome immune checkpoint resistance in melanoma. 2023, a928-a928. DOI: 10.1136/jitc-2023-sitc2023.0830.Peer-Reviewed Original ResearchMacrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB- but not chemically induced non-melanoma skin cancer
Huth S, Huth L, Heise R, Marquardt Y, Lopopolo L, Piecychna M, Boor P, Fingerle-Rowson G, Kapurniotu A, Yazdi A, Bucala R, Bernhagen J, Baron J. Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB- but not chemically induced non-melanoma skin cancer. Scientific Reports 2023, 13: 11611. PMID: 37464010, PMCID: PMC10354066, DOI: 10.1038/s41598-023-38748-9.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorNon-melanoma skin cancerD-DTSkin cancerRecombinant macrophage migration inhibitory factorUVB irradiationAcute UVB irradiationPrevention of photocarcinogenesisMigration inhibitory factorAccumulation of macrophagesAdditive protective effectChronic UVB irradiationDouble knockout micePotential therapeutic targetMacrophage accumulationCommon cancerPathophysiological roleProtective effectSkin tumorsKnockout miceTherapeutic targetInhibitory factorGenetic deletionCytokinesCancerThe SNP rs755622 is associated with immune activation in glioblastoma
Alban T, Grabowski M, Otvos B, Bayik D, Wang W, Zalavadia A, Makarav V, Troike K, McGraw M, Rabljenovic A, Lauko A, Neumann C, Roversi G, Waite K, Cioffi G, Patil N, Tran T, McCortney K, Steffens A, Diaz-Montero C, Brown J, Egan K, Horbinski C, Barnholtz-Sloan J, Rajappa P, Vogelbaum M, Bucala R, Chan T, Ahluwalia M, Lathia J. The SNP rs755622 is associated with immune activation in glioblastoma. JCI Insight 2023, 8: e160024. PMID: 37252795, PMCID: PMC10371339, DOI: 10.1172/jci.insight.160024.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorImmune activationCytokine macrophage migration inhibitory factorMigration inhibitory factorLactotransferrin (LTF) expressionLeukocyte infiltrationHallmark of glioblastomaImmune microenvironmentTreatment responseRs755622Inhibitory factorDrug resistanceGermline mutationsIntratumoral heterogeneityTumoral microenvironmentGermline SNPsGlioblastomaUrothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain
Ye S, Mahmood D, Ma F, Leng L, Bucala R, Vera P. Urothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain. Cells 2023, 12: 1440. PMID: 37408274, PMCID: PMC10217556, DOI: 10.3390/cells12101440.Peer-Reviewed Original ResearchConceptsHigh mobility group box 1Macrophage migration inhibitory factorBladder painOxidative stressDisulfide HMGB1Mobility group box 1MIF-deficient miceNovel potential therapeutic strategyMigration inhibitory factorGroup box 1Potential therapeutic strategyOxidative stress productionN-acetylcysteine amideERK activationIntravesical treatmentMicturition volumeMicturition parametersReceptor 4Mechanical thresholdPainTherapeutic strategiesBox 1Bladder tissueInhibitory factorWestern blot
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 ResearchConceptsMacrophage 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 cellsTranscriptionGenesMacrophage migration inhibitory factor regulates specific innate immune sensor responses in gingival epithelial cells
Kantrong N, Chang AM, Bamashmous S, Hajjar AM, Bucala RJ, Darveau RP. Macrophage migration inhibitory factor regulates specific innate immune sensor responses in gingival epithelial cells. The Journal Of Periodontology 2022, 93: 1940-1950. PMID: 35100435, DOI: 10.1002/jper.21-0598.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorGingival epithelial cellsIL-8/CXCL8Migration inhibitory factorGingival tissuesJunctional epitheliumGingival epitheliumRole of MIFInhibitory factorMIF KO miceEpithelial cellsExpression of TLR4Healthy gingival tissuesToll-like receptorsInterleukin-1 receptorRepertoire of receptorsOral healthNeutrophil chemoattractantIL-1R1IL-1R2Neutrophil regulationKO micePeriodontal tissuesIL-1ROral homeostasis
2021
Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR
Sánchez-Zuno GA, Bucala R, Hernández-Bello J, Román-Fernández IV, García-Chagollán M, Nicoletti F, Matuz-Flores MG, García-Arellano S, Esparza-Michel JA, Cerpa-Cruz S, Pérez-Guerrero EE, Muñoz-Valle JF. Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR. Journal Of Clinical Medicine 2021, 11: 120. PMID: 35011861, PMCID: PMC8745239, DOI: 10.3390/jcm11010120.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorHigh disease activityDisease activityDAS28-ESRControl subjectsClinical activityRA clinical activityRheumatoid arthritis patientsExpression of CD74Expression of CXCR4Migration inhibitory factorScavenger-type receptorsDifferent clinical activitiesRA patientsMIF receptorArthritis pathogenesisArthritis patientsCXCR7 expressionInflammatory conditionsReceptor expressionPatientsB cellsDecoy receptorInhibitory factorSoluble CD74Macrophage migration inhibitory factor exerts pro-proliferative and anti-apoptotic effects via CD74 in murine hepatocellular carcinoma
Wirtz T, Saal A, Bergmann I, Fischer P, Heinrichs D, Brandt E, Koenen M, Djudjaj S, Schneider K, 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. Zeitschrift Für Gastroenterologie 2021, 59: e206-e207. DOI: 10.1055/s-0041-1733611.Peer-Reviewed Original ResearchICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the MIF Immune Susceptibility Locus
Yao J, Leng L, Fu W, Li J, Bronner C, Bucala R. ICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the MIF Immune Susceptibility Locus. Arthritis & Rheumatology 2021, 73: 1931-1942. PMID: 33844457, DOI: 10.1002/art.41753.Peer-Reviewed Original ResearchMeSH KeywordsAllelesApoptosisCCAAT-Enhancer-Binding ProteinsCell LineFibroblastsGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenotypeGlucocorticoidsHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsPromoter Regions, GeneticReceptors, GlucocorticoidUbiquitin-Protein LigasesConceptsMacrophage migration inhibitory factorAutoimmune disease severityMIF -794 CATTRheumatoid synovial fibroblastsMIF expressionGlucocorticoid receptorGlucocorticoid sensitivitySynovial fibroblastsT cellsDisease severityPeripheral blood T cellsBlood T cellsMigration inhibitory factorGlucocorticoid-treated cellsAP-1Glucocorticoid immunosuppressionMIF promoterMIF genotypeMIF polymorphismsFactor antibodyInflammatory responseT lymphocytesActivator protein-1Glucocorticoid responsivenessInhibitory factorMacrophage 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 ResearchConceptsMacrophage 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 target197-LB: The Regulation of HSL by Macrophage Migration Inhibitory Factor (MIF) Contributes to Adipocyte Hypertrophy and Development of Obesity
CHEN L, HUANG Y, LI L, ZABIHI H, QI Y, LENG L, SUN G, BUCALA R, QI D. 197-LB: The Regulation of HSL by Macrophage Migration Inhibitory Factor (MIF) Contributes to Adipocyte Hypertrophy and Development of Obesity. Diabetes 2021, 70 DOI: 10.2337/db21-197-lb.Peer-Reviewed Original ResearchRole of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis
Poulsen KL, Fan X, Kibler CD, Huang E, Wu X, McMullen MR, Leng L, Bucala R, Ventura-Cots M, Argemi J, Bataller R, Nagy LE. Role of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis. JCI Insight 2021, 6: e141420. PMID: 33945507, PMCID: PMC8262327, DOI: 10.1172/jci.insight.141420.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorAlcohol-associated hepatitisChemokine expressionHealthy controlsLiver diseaseRole of MIFMIF KO miceChronic liver diseaseCytokines/chemokinesMigration inhibitory factorUpstream regulatorChemokine signatureChemokine CCL20WT miceCultured hepatocytesMultiple chemokinesChemokine systemInflammatory responseChemokine membersNovel therapiesEthanol feedingPatientsChemokine familyChemokinesInhibitory factorCD74 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 maintenance