2024
Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose
Bloom J, Pantouris G, He M, Aljabari B, Mishra L, Manjula R, Parkins A, Lolis E, Al-Abed Y. Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose. Molecular Medicine 2024, 30: 43. PMID: 38539088, PMCID: PMC10976746, DOI: 10.1186/s10020-024-00803-0.Peer-Reviewed Original ResearchMeSH KeywordsAcetaminophenAnimalsBenzopyransChemical and Drug Induced Liver InjuryChromonesDisease Models, AnimalHydrogen PeroxideKineticsLiverMacrophage Migration-Inhibitory FactorsMiceOxidative StressSulfonamidesConceptsMode of inhibitionAllosteric inhibitorsActive site pocketMigration inhibitory factorSite pocketInhibitory factorProtein crystallographyTautomerase active siteOxidative stressT-614Murine modelDrug modePleiotropic cytokineNon-competitive type of inhibitionAPAP overdoseActive siteMacrophage migration inhibitory factorInhibition constantType of inhibitionInhibitor of macrophage migration inhibitory factorKinetic analysisBackgroundMacrophage migration inhibitory factorAcetaminophen overdoseIn vivo experimentsMultiple small molecule inhibitors
2023
Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells
Spiller L, Manjula R, Leissing F, Basquin J, Bourilhon P, Sinitski D, Brandhofer M, Levecque S, Gerra S, Sabelleck B, Zhang L, Feederle R, Flatley A, Hoffmann A, Panstruga R, Bernhagen J, Lolis E. Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells. Science Signaling 2023, 16: eadg2621. PMID: 37988455, DOI: 10.1126/scisignal.adg2621.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMammalsNeutrophilsPlant ProteinsReceptors, CXCR4Saccharomyces cerevisiaeConceptsMammalian macrophage migration inhibitory factorHetero-oligomeric complexesHigh structural similarityMultifunctional inflammatory cytokineHuman lung epithelial cellsYeast reporter systemReporter systemLung epithelial cellsPlant leavesFunctional similarityCellular responsesHuman cellsPharmacological inhibitorsDopachrome tautomeraseFunctional implicationsX-ray crystallographyMacrophage migration inhibitory factorStructural similarityEpithelial cellsMigration inhibitory factorCXCR4 receptorProteinTautomerase activityCellsMIF receptorMapping N- to C-terminal allosteric coupling through disruption of a putative CD74 activation site in D-dopachrome tautomerase
Chen E, Widjaja V, Kyro G, Allen B, Das P, Prahaladan V, Bhandari V, Lolis E, Batista V, Lisi G. Mapping N- to C-terminal allosteric coupling through disruption of a putative CD74 activation site in D-dopachrome tautomerase. Journal Of Biological Chemistry 2023, 299: 104729. PMID: 37080391, PMCID: PMC10208890, DOI: 10.1016/j.jbc.2023.104729.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, Differentiation, B-LymphocyteBinding SitesHistocompatibility Antigens Class IIHumansInflammationMacrophage Migration-Inhibitory Factors
2018
Nanosecond Dynamics Regulate the MIF‐Induced Activity of CD74
Pantouris G, Ho J, Shah D, Syed MA, Leng L, Bhandari V, Bucala R, Batista VS, Loria JP, Lolis E. Nanosecond Dynamics Regulate the MIF‐Induced Activity of CD74. Angewandte Chemie International Edition 2018, 57: 7116-7119. PMID: 29669180, PMCID: PMC6282165, DOI: 10.1002/anie.201803191.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAntigens, Differentiation, B-LymphocyteHistocompatibility Antigens Class IIHumansInflammationIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMolecular Dynamics SimulationProtein Conformation, beta-Strand
2016
Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions*
Rajasekaran D, Gröning S, Schmitz C, Zierow S, Drucker N, Bakou M, Kohl K, Mertens A, Lue H, Weber C, Xiao A, Luker G, Kapurniotu A, Lolis E, Bernhagen J. Macrophage Migration Inhibitory Factor-CXCR4 Receptor Interactions*. Journal Of Biological Chemistry 2016, 291: 15881-15895. PMID: 27226569, PMCID: PMC4957068, DOI: 10.1074/jbc.m116.717751.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsChemokine CXCL12CHO CellsCricetinaeCricetulusHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsReceptors, CXCR4Recombinant ProteinsConceptsMacrophage migration inhibitory factorChemokine receptorsCXCR4 receptorRole of MIFMIF's biological activityMigration inhibitory factorChemokine receptor interactionsFunctional CXCR4 receptorsClassical chemokine receptorsChemokine-like activityPartial allosteric agonistRegions of CXCR4Inflammatory cytokinesReceptor CD74Leukocyte recruitmentAllosteric agonistInhibitory factorCXCR4Non-cognate interactionsReceptorsPharmacological reagentsReceptor interactionArray analysisGenetic strainsCritical biological responses
2001
Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery
Lolis E. Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery. Current Opinion In Pharmacology 2001, 1: 662-668. PMID: 11757824, DOI: 10.1016/s1471-4892(01)00112-6.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsCOP9 Signalosome ComplexDNA-Binding ProteinsDrug DesignGenes, p53GlucocorticoidsHumansInflammationInflammation MediatorsIntracellular Signaling Peptides and ProteinsMacrophage Migration-Inhibitory FactorsMembrane ProteinsMolecular Sequence DataNeoplasmsNeovascularization, PathologicPeptide HydrolasesPhosphoproteinsStructure-Activity RelationshipTranscription FactorsConceptsMacrophage migration inhibitory factorMigration inhibitory factorContribution of MIFInhibitory factorElevated MIF levelsMIF's biological activityActivity of CD4Natural killer cellsInflammatory neurological diseasesInflammatory lung diseasesMIF levelsUlcerative colitisKiller cellsRheumatoid arthritisLung diseaseInflammatory diseasesT cellsHuman studiesNeurological diseasesTherapeutic interventionsDiseaseEndothelial cellsNumber of diseasesIntracellular regulatory proteinsCancerDevelopment of chronic colitis is dependent on the cytokine MIF
de Jong Y, Abadia-Molina A, Satoskar A, Clarke K, Rietdijk S, Faubion W, Mizoguchi E, Metz C, Sahli M, ten Hove T, Keates A, Lubetsky J, Farrell R, Michetti P, van Deventer S, Lolis E, David J, Bhan A, Terhorst C. Development of chronic colitis is dependent on the cytokine MIF. Nature Immunology 2001, 2: 1061-1066. PMID: 11668338, DOI: 10.1038/ni720.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesBone Marrow TransplantationChronic DiseaseColitisCrohn DiseaseDNA-Binding ProteinsFemaleHumansImmunization, PassiveLipopolysaccharidesMacrophage ActivationMacrophage Migration-Inhibitory FactorsMaleMiceMice, KnockoutModels, AnimalNuclear ProteinsRadiation ChimeraWeight LossConceptsMacrophage migration inhibitory factorCytokine macrophage migration inhibitory factorMIF-deficient miceCrohn's diseaseRole of MIFImmune systemPlasma MIF concentrationMucosal immune systemInnate immune cellsInnate immune systemChronic colitisMIF concentrationsExperimental colitisMIF productionMurine colitisImmune cellsColitisIntestinal bacteriaInhibitory factorDiseaseNew targetsMiceLipopolysaccharideCell typesPatients
1999
Pro-1 of Macrophage Migration Inhibitory Factor Functions as a Catalytic Base in the Phenylpyruvate Tautomerase Activity † , ‡
Lubetsky J, Swope M, Dealwis C, Blake P, Lolis E. Pro-1 of Macrophage Migration Inhibitory Factor Functions as a Catalytic Base in the Phenylpyruvate Tautomerase Activity † , ‡. Biochemistry 1999, 38: 7346-7354. PMID: 10353846, DOI: 10.1021/bi990306m.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBinding SitesCatalysisCrystallography, X-RayEnzyme ActivationGlycineHumansHydrogen-Ion ConcentrationIntramolecular OxidoreductasesMacromolecular SubstancesMacrophage Migration-Inhibitory FactorsMethionineMutagenesis, Site-DirectedNuclear Magnetic Resonance, BiomolecularPhenylpyruvic AcidsProlineRecombinant ProteinsConceptsMacrophage migration inhibitory factorMacrophage migration inhibitory factor (MIF) functionsAnti-inflammatory effectsMigration inhibitory factorImportant immunoregulatory moleculeTautomerase activityImmunoregulatory moleculesPhenylpyruvate tautomerase activityInhibitory factorP-hydroxyphenylpyruvateGlucocorticoidsPro-1CytokinesActivityMacrophage migration inhibitory factor: Cytokine, hormone, or enzyme?
Swope M, Lolis E. Macrophage migration inhibitory factor: Cytokine, hormone, or enzyme? 1999, 139: 1-32. PMID: 10453691, DOI: 10.1007/bfb0033647.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsCytokinesEnzymesHormonesHumansMacrophage Migration-Inhibitory FactorsMolecular Sequence DataProtein ConformationSequence Homology, Amino Acid
1998
Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor
Swope M, Sun H, Blake P, Lolis E. Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor. The EMBO Journal 1998, 17: 3534-3541. PMID: 9649424, PMCID: PMC1170690, DOI: 10.1093/emboj/17.13.3534.Peer-Reviewed Original ResearchConceptsN-terminal prolineN-terminal regionStructure-based inhibitorsMultiple sequence alignmentThree-dimensional structureInvariant residuesEntire polypeptideMicrobial enzymesCatalytic basePro-1Sequence alignmentMIF homologuesCytokine activityHuman macrophage migration inhibitory factorCatalytic siteProlineInhibitory factorHomologuesUnderlying biological activityP-hydroxyphenylpyruvateProteinMacrophage migration inhibitory factorActive siteBiological activityMacrophage Migration Inhibitory Factor Interactions with Glutathione and S -Hexylglutathione*
Swope M, Sun H, Klockow B, Blake P, Lolis E. Macrophage Migration Inhibitory Factor Interactions with Glutathione and S -Hexylglutathione*. Journal Of Biological Chemistry 1998, 273: 14877-14884. PMID: 9614090, DOI: 10.1074/jbc.273.24.14877.Peer-Reviewed Original ResearchBinding SitesCircular DichroismEnzyme InhibitorsFluorescenceGlutathioneHumansHydrogen-Ion ConcentrationIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMagnetic Resonance SpectroscopyModels, MolecularProtein BindingProtein ConformationProtein FoldingRecombinant ProteinsSulfhydryl Compounds
1996
The subunit structure of human macrophage migration inhibitory factor: evidence for a trimer
Sun H, Swope M, Craig C, Bedarkar S, Bernhagen J, Bucala R, Lolis E. The subunit structure of human macrophage migration inhibitory factor: evidence for a trimer. Protein Engineering Design And Selection 1996, 9: 631-635. PMID: 8875640, DOI: 10.1093/protein/9.8.631.Peer-Reviewed Original ResearchCrystallizationCrystallography, X-RayHumansMacrophage Migration-Inhibitory FactorsMass SpectrometryProtein ConformationRecombinant ProteinsScattering, RadiationSelenomethionine