Featured Publications
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 AgedPulmonary Disease, Chronic ObstructiveReceptors, ImmunologicSmokeSmokingTobaccoTumor 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 structuresEndothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury
Sauler M, Zhang Y, Min J, Leng L, Shan P, Roberts S, Jorgensen WL, Bucala R, Lee PJ. Endothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury. The FASEB Journal 2015, 29: 1940-1949. PMID: 25609432, PMCID: PMC4415022, DOI: 10.1096/fj.14-260299.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLung endothelial cellsMurine lung endothelial cellsLung injuryEndothelial cellsProtective effectExogenous MIFCD74 deficient miceCD74-dependent mannerHours of hyperoxiaMIF receptor CD74Acute lung injuryHyperoxic lung injuryBronchoalveolar lavage proteinMigration inhibitory factorBronchoalveolar proteinMIF deficiencyMedian survivalEndothelial injuryWT miceAcute oxidative stressReceptor CD74Lavage proteinReceptor antagonistReceptor inhibitorsCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2022
Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury
Harris ZM, Sun Y, Joerns J, Clark B, Hu B, Korde A, Sharma L, Shin HJ, Manning EP, Placek L, Unutmaz D, Stanley G, Chun H, Sauler M, Rajagopalan G, Zhang X, Kang MJ, Koff JL. Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury. Oxidative Medicine And Cellular Longevity 2022, 2022: 9518592. PMID: 36193076, PMCID: PMC9526641, DOI: 10.1155/2022/9518592.Peer-Reviewed Original ResearchConceptsAcute lung injuryEpidermal growth factor receptorAlveolar epithelial cellsLung injurySevere hyperoxiaEGFR inhibitionEpithelial cellsHyperoxia-Induced Lung InjuryRole of EGFRMurine alveolar epithelial cellsGrowth factor receptor inhibitionWorse clinical outcomesEpidermal growth factor receptor inhibitionHuman alveolar epithelial cellsWild-type littermatesPoly (ADP-ribose) polymeraseTerminal dUTP nickGrowth factor receptorClinical outcomesImproved survivalReceptor inhibitionLung repairProtective roleComplex roleEGFR deletion
2021
MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model
Tilstam PV, Schulte W, Holowka T, Kim BS, Nouws J, Sauler M, Piecychna M, Pantouris G, Lolis E, Leng L, Bernhagen J, Fingerle-Rowson G, Bucala R. MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model. Journal Of Clinical Investigation 2021, 131: e127171. PMID: 34850744, PMCID: PMC8631602, DOI: 10.1172/jci127171.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesDisease Models, AnimalFemaleFlow CytometryGene Expression ProfilingInflammationIntramolecular OxidoreductasesLeukocyte CountMacrophage Migration-Inhibitory FactorsMacrophagesMacrophages, PeritonealMaleMiceMice, Inbred C57BLMice, TransgenicPeritoneal LavagePhenotypeProtein BindingRNA-SeqSepsisSignal TransductionConceptsMacrophage migration inhibitory factorSmall peritoneal macrophagesLarge peritoneal macrophagesPolymicrobial sepsisPeritoneal macrophagesMIF receptor CD74MIF promoter polymorphismsMIF-2Migration inhibitory factorPolymicrobial sepsis modelMIF deficiencyAdoptive transferSeptic shockSurvival benefitInfectious insultsMIF antibodyExcessive inflammationInflammatory cytokinesReceptor CD74Sepsis modelProtective effectPeritoneal cavityDifferent infectionsPromoter polymorphismInflammatory macrophagesMetformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment.
Polverino F, Wu TD, Rojas-Quintero J, Wang X, Mayo J, Tomchaney M, Tram J, Packard S, Zhang D, Cleveland KH, Cordoba-Lanus E, Owen CA, Fawzy A, Kinney GL, Hersh CP, Hansel NN, Doubleday K, Sauler M, Tesfaigzi Y, Ledford JG, Casanova C, Zmijewski J, Konhilas J, Langlais PR, Schnellmann R, Rahman I, McCormack M, Celli B. Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment. American Journal Of Respiratory And Critical Care Medicine 2021, 204: 651-666. PMID: 34033525, PMCID: PMC8521702, DOI: 10.1164/rccm.202012-4510oc.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseMetformin useEmphysema progressionEmphysematous chronic obstructive pulmonary diseaseOxidative stressSmall airway remodelingProtective actionEfficacy of metforminObstructive pulmonary diseaseCigarette smoke inhalationPercentage of emphysemaER stressEndoplasmic reticulum stressEmphysema treatmentAirway remodelingPulmonary diseasePulmonary inflammationAirspace enlargementClinical evidenceLung agingAge-related diseasesSmoke inhalationClinical trialsMuscle injuryMetformin effects
2020
Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF‐2 in adipose tissue during endotoxemia
Kim B, Tilstam PV, Arnke K, Leng L, Ruhl T, Piecychna M, Schulte W, Sauler M, Frueh FS, Storti G, Lindenblatt N, Giovanoli P, Pallua N, Bernhagen J, Bucala R. Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF‐2 in adipose tissue during endotoxemia. The FASEB Journal 2020, 34: 4219-4233. PMID: 31961019, PMCID: PMC7060131, DOI: 10.1096/fj.201901511r.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorWhite adipose tissueAdipose tissue macrophagesAdipose tissueElevated macrophage migration inhibitory factorInflammatory cytokine macrophage migration inhibitory factorVisceral white adipose tissueCytokine macrophage migration inhibitory factorPro-inflammatory macrophage polarizationMIF family proteinsPro-inflammatory phenotypeAnti-inflammatory phenotypeMIF-2Migration inhibitory factorWild-type miceHuman adipose tissueMurine endotoxemia modelMIF cytokineMIF deficiencySystemic inflammationDifferential regulationHealthy patientsEndotoxemia modelPeritoneal fluidLeading cause
2019
Endothelial toll‐like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a
Kim S, Shan P, Hwangbo C, Zhang Y, Min J, Zhang X, Ardito T, Li A, Peng T, Sauler M, Lee PJ. Endothelial toll‐like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a. Aging Cell 2019, 18: e12914. PMID: 30790400, PMCID: PMC6516428, DOI: 10.1111/acel.12914.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Senescence-related gene expressionLung integritySenescence-associated genesReceptor 4New functional roleLung ECsInnate immune receptor toll-like receptor 4Immune receptor toll-like receptor 4Role of TLR4Endothelial Toll-like receptor 4Receptor Toll-like receptor 4Epigenetic regulationHistone H4Epigenetic suppressionTLR4-/- miceGene expressionEndogenous p16Molecular mechanismsWild-type miceNovel roleExpression of p16Lung endothelial cellsFunctional roleDistinct roles
2018
BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation
Britto CJ, Niu N, Khanal S, Huleihel L, Herazo-Maya J, Thompson A, Sauler M, Slade MD, Sharma L, Dela Cruz CS, Kaminski N, Cohn LE. BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l321-l333. PMID: 30461288, PMCID: PMC6397348, DOI: 10.1152/ajplung.00056.2018.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsGlycoproteinsInflammationLipopolysaccharidesLungMice, Inbred C57BLNeutrophil InfiltrationPhosphoproteinsConceptsLung inflammationAcute inflammationC motif chemokine ligand 10Lung neutrophil recruitmentRegulation of CXCL10Acute lung inflammationBronchoalveolar lavage concentrationsChemokine ligand 10Innate immune responseIFN regulatory factorIntranasal LPSLavage concentrationsLung recruitmentNeutrophil recruitmentWT miceImmune effectsLung diseasePMN recruitmentInflammatory responseLPS treatmentLung tissueInflammatory signalsImmune responseImmunomodulatory propertiesInflammation
2016
D‐dopachrome tautomerase in adipose tissue inflammation and wound repair
Kim B, Tilstam PV, Hwang SS, Simons D, Schulte W, Leng L, Sauler M, Ganse B, Averdunk L, Kopp R, Stoppe C, Bernhagen J, Pallua N, Bucala R. D‐dopachrome tautomerase in adipose tissue inflammation and wound repair. Journal Of Cellular And Molecular Medicine 2016, 21: 35-45. PMID: 27605340, PMCID: PMC5192814, DOI: 10.1111/jcmm.12936.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsAntigens, Differentiation, B-LymphocyteCell MovementCell ProliferationDown-RegulationFibroblastsHistocompatibility Antigens Class IIHumansInflammationIntramolecular OxidoreductasesMacrophagesMaleMiceMice, Inbred C57BLObesityReceptors, CXCR4Receptors, Interleukin-8BUp-RegulationWound HealingConceptsAdipose tissue inflammationSubcutaneous adipose tissueD-DTAdipose tissueTissue inflammationWound repairEpididymal fat padsDopachrome tautomeraseReceptor CXCR2MIF antibodyInflammatory cellsReceptor CD74Healthy donorsReceptor expressionFat padMRNA expressionProtein levelsWound healingFibroblast survivalMIFInflammationHealingTissueCell migrationFibroblast wound healing