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 ResearchConceptsMode 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
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 translationIL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer
Wang L, Miyahira A, Simons D, Lu X, Chang A, Wang C, Suni M, Maino V, Dirbas F, Yim J, Waisman J, Lee P. IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer. Cancer Research 2017, 77: 1119-1126. PMID: 27879265, PMCID: PMC5334262, DOI: 10.1158/0008-5472.can-16-1373.Peer-Reviewed Original ResearchConceptsPeripheral blood T cellsBreast cancer patientsBlood T cellsCancer patientsT cellsIL6 levelsWorse relapse-free survivalPlasma IL6 levelsCancer cellsRelapse-free survivalSerum IL6 levelsAnti-inflammatory propertiesHost immune responseInvolved downregulationClinical outcomesPredictive biomarkersImmune responsePleiotropic cytokinePatientsIL6Cancer ResCancer progressionSurvivalDiagnosisCells
2014
Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease
Sauler M, Leng L, Trentalange M, Haslip M, Shan P, Piecychna M, Zhang Y, Andrews N, Mannam P, Allore H, Fried T, Bucala R, Lee PJ. Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2014, 306: l487-l496. PMID: 24441872, PMCID: PMC3949087, DOI: 10.1152/ajplung.00284.2013.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedAged, 80 and overAnimalsApoptosisCellular SenescenceCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21EmphysemaFemaleHumansIntramolecular OxidoreductasesLungMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedNicotianaPulmonary Disease, Chronic ObstructiveReceptors, ImmunologicSmokeSmokingTumor Suppressor Protein p53Young AdultConceptsChronic obstructive pulmonary diseaseMacrophage migration inhibitory factorPathogenesis of COPDDevelopment of COPDMIF receptor CD74Obstructive pulmonary diseasePulmonary diseaseWT miceReceptor CD74Role of MIFMacrophage migration inhibitory factor deficiencyMigration inhibitory factorNormal alveolar structureMo of ageWild-type controlsMIF concentrationsFormer smokersLung volumePlasma concentrationsSpontaneous emphysemaFactor deficiencyCigarette smokePleiotropic cytokineInhibitory factorAlveolar structures
2012
Expression of the p53 Target CDIP Correlates with Sensitivity to TNFα-Induced Apoptosis in Cancer Cells
Brown-Endres L, Schoenfeld D, Tian F, Kim HG, Namba T, Muñoz-Fontela C, Mandinova A, Aaronson SA, Lee SW. Expression of the p53 Target CDIP Correlates with Sensitivity to TNFα-Induced Apoptosis in Cancer Cells. Cancer Research 2012, 72: 2373-2382. PMID: 22549949, PMCID: PMC3349239, DOI: 10.1158/0008-5472.can-11-3369.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisApoptosis Regulatory ProteinsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansInterleukin-8MAP Kinase Kinase 4MAP Kinase Signaling SystemMiceMice, NudeNF-kappa BReactive Oxygen SpeciesRecombinant ProteinsTumor Necrosis Factor-alphaTumor Suppressor Protein p53ConceptsApoptotic cell fateCell fateCancer cellsP53-mediated deathGenotoxic stressAntiapoptotic programGrowth-suppressive effectsJNK activationApoptotic pathwaySurvival responseApoptosisDual roleExpression correlatesCellsCDIPPathwayPleiotropic cytokineFateExpressionPredictive biomarkersTNFαRegulatorDeathSurvivalActivationIL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice
Rankin AL, Guay H, Herber D, Bertino SA, Duzanski TA, Carrier Y, Keegan S, Senices M, Stedman N, Ryan M, Bloom L, Medley Q, Collins M, Nickerson-Nutter C, Craft J, Young D, Dunussi-Joannopoulos K. IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice. The Journal Of Immunology 2012, 188: 1656-1667. PMID: 22231702, PMCID: PMC3618484, DOI: 10.4049/jimmunol.1003871.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoimmunityB-LymphocytesCD4-Positive T-LymphocytesCell DifferentiationInterferon-gammaInterleukinsLupus Erythematosus, SystemicLymphatic DiseasesLymphocyte ActivationMiceMice, Inbred MRL lprMice, KnockoutReceptors, Interleukin-21SkinSplenomegalyT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerConceptsT cell effector subsetsIL-21Effector subsetsIL-21RT cellsHelper cellsSpontaneous germinal center formationIL-21-dependent mannerIL-21 receptorMRL/MpJPlasma cell accumulationGerminal center formationTh cell differentiationSignificant reductionAutoantibody titersAutoantibody productionCytokines IFNImmune activationSystemic autoimmunityJ miceDisease manifestationsT lymphocytesPleiotropic cytokineB cellsDisease pathogenesis
2005
IL-6 and Its Circadian Secretion in Humans
Vgontzas A, Bixler E, Lin H, Prolo P, Trakada G, Chrousos G. IL-6 and Its Circadian Secretion in Humans. NeuroImmunoModulation 2005, 12: 131-140. PMID: 15905620, DOI: 10.1159/000084844.Peer-Reviewed Original ResearchConceptsBiphasic circadian patternInterleukin-6Disorders of excessive daytime sleepinessCircadian patternCircadian secretionObstructive sleep apneaShort-term sleep lossIL-6 levelsExcessive daytime sleepinessBody mass indexInterleukin-6 secretionStress system activitySleep apneaYoung adultsNonimmune cellsMass indexPathophysiological mechanismsDaytime sleepinessSleep-deprived individualsCortisol secretionHealthy individualsPleiotropic cytokineSleep/wake cycleSleep deprivationSleepiness
2004
Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2
Lainez B, Fernandez-Real J, Romero X, Esplugues E, Cañete J, Ricart W, Engel P. Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2. International Immunology 2004, 16: 169-177. PMID: 14688072, DOI: 10.1093/intimm/dxh014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlternative SplicingAnimalsArthritis, RheumatoidBase SequenceChlorocebus aethiopsCloning, MolecularCOS CellsEnzyme-Linked Immunosorbent AssayEtanerceptFemaleHumansImmunoglobulin GMaleMiddle AgedMolecular Sequence DataProtein IsoformsReceptors, Tumor Necrosis FactorSepsisTransfectionTumor Necrosis Factor-alphaConceptsAlternative splicingCell death inductionTNF-alpha-induced apoptosisExtracellular ectodomainMultiple inflammatory pathologiesCytoplasmic domainNovel isoformHuman TNFR2COS cellsExpression studiesDeath inductionCell typesTNF-alpha functionReceptors TNFR1SplicingExon 7Soluble formIsoformsBiological effectsBiological activityTumor necrosis factor receptor 2Pleiotropic cytokineNecrosis factor receptor 2Factor receptor 2TNFR2
1999
Microglial Activation Varies in Different Models of Creutzfeldt-Jakob Disease
Baker C, Lu Z, Zaitsev I, Manuelidis L. Microglial Activation Varies in Different Models of Creutzfeldt-Jakob Disease. Journal Of Virology 1999, 73: 5089-5097. PMID: 10233972, PMCID: PMC112554, DOI: 10.1128/jvi.73.6.5089-5097.1999.Peer-Reviewed Original ResearchConceptsCreutzfeldt-Jakob diseaseLysosomal protease cathepsin SCathepsin SMRNA expressionAbnormal PrP formationHost mRNA expressionUpregulation of CCR5Chemokine receptor CCR5Glial cell involvementGrowth factor beta1Microglial transcriptsNeuronal destructionProtease cathepsin SMicroglial activationAmyloid depositionPathogenetic pathwaysReceptor CCR5Cell involvementRodent modelsChronic reservoirDistinctive neuropathologyPleiotropic cytokineTGF-beta1Primary sitePrP pathology
1998
Leukemia Inhibitory Factor in Human Reproduction
Senturk L, Arici A. Leukemia Inhibitory Factor in Human Reproduction. American Journal Of Reproductive Immunology 1998, 39: 144-151. PMID: 9506212, DOI: 10.1111/j.1600-0897.1998.tb00346.x.Peer-Reviewed Original ResearchConceptsLeukemia inhibitory factorFallopian tubeMenstrual cycleHuman endometriumMenstrual cycle-dependent mannerInhibitory factorRole of LIFEffects of LIFHuman reproductionEndometrial LIF expressionMyeloid leukemic cell linesTime of implantationTime of ovulationLIF levelsOvulatory eventsLIF expressionInterleukin-6 familyStromal cell culturesEndometrial tissueInflammatory cytokinesLeukemic cell linesPeripheral neuronsPleiotropic cytokineSuccessful implantationOvarian follicles
1994
Epithelial interleukin-11. Regulation by cytokines, respiratory syncytial virus, and retinoic acid.
Elias J, Zheng T, Einarsson O, Landry M, Trow T, Rebert N, Panuska J. Epithelial interleukin-11. Regulation by cytokines, respiratory syncytial virus, and retinoic acid. Journal Of Biological Chemistry 1994, 269: 22261-22268. PMID: 8071352, DOI: 10.1016/s0021-9258(17)31785-4.Peer-Reviewed Original ResearchConceptsRespiratory syncytial virusIL-11 productionIL-11 protein productionIL-1IL-11Retinoic acidSyncytial virusSimplex virus type 2Growth factorIL-11 mRNADose-dependent fashionVirus type 2Hepatocyte growth factorStimulus-specific fashionIL-6IL-4IL-7Alveolar A549 cellsPleiotropic cytokineType 2Human alveolar A549 cellsInterleukin-11Epithelial cellsA549 cellsUnstimulated cells
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