2019
Low ambient humidity impairs barrier function and innate resistance against influenza infection
Kudo E, Song E, Yockey LJ, Rakib T, Wong PW, Homer RJ, Iwasaki A. Low ambient humidity impairs barrier function and innate resistance against influenza infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 10905-10910. PMID: 31085641, PMCID: PMC6561219, DOI: 10.1073/pnas.1902840116.Peer-Reviewed Original ResearchConceptsInfluenza infectionImpair barrier functionImpairs host defenseSeasonal influenza virusesInfluenza virus infectionLungs of miceImpairs mucociliary clearanceTissue repairInduction of IFNInnate antiviral defenseViral burdenMucociliary clearanceDisease outcomeRespiratory challengeVirus infectionSevere diseaseViral infectionCongenic miceHost responseViral transmissionHost defenseSingle-cell RNA sequencingInnate resistanceDisease pathologyInfluenza virus
2016
Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling
Bruscia E, Zhang P, Barone C, Scholte BJ, Homer R, Krause D, Egan ME. Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2016, 310: l711-l719. PMID: 26851259, PMCID: PMC4836110, DOI: 10.1152/ajplung.00284.2015.Peer-Reviewed Original ResearchConceptsLung pathologyCF miceImmune responseWT miceChronic inflammationCystic fibrosisAbnormal immune responseChronic pulmonary infectionPersistent immune responseWild-type littermatesCF mouse modelsPseudomonas aeruginosa lipopolysaccharideCF lung pathologyPulmonary infectionChronic administrationLPS exposurePersistent inflammationLung remodelingWT littermatesLung tissueOverall pathologyMouse modelInflammationChronic exposureBacterial products
2011
IFN-γ Acts on the Airway Epithelium To Inhibit Local and Systemic Pathology in Allergic Airway Disease
Mitchell C, Provost K, Niu N, Homer R, Cohn L. IFN-γ Acts on the Airway Epithelium To Inhibit Local and Systemic Pathology in Allergic Airway Disease. The Journal Of Immunology 2011, 187: 3815-3820. PMID: 21873527, PMCID: PMC3178669, DOI: 10.4049/jimmunol.1100436.Peer-Reviewed Original ResearchConceptsAirway epitheliumAllergic airway inflammationAllergic airway diseaseTh2 cell activationGoal of therapyProduction of IFNAdministration of medicationsSystemic side effectsAirway mucosal surfaceAirway epithelial cellsSites of inflammationIFN-γ actionAirway inflammationAirway obstructionPersistent asthmaRefractory asthmaAirway diseaseIFN-γRTh1 cellsPathological responseSystemic pathologyEffector functionsSide effectsBone marrowAsthmaAirway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway
Mijares LA, Wangdi T, Sokol C, Homer R, Medzhitov R, Kazmierczak BI. Airway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway. The Journal Of Immunology 2011, 186: 7080-7088. PMID: 21572023, PMCID: PMC3110630, DOI: 10.4049/jimmunol.1003687.Peer-Reviewed Original ResearchConceptsInnate immune responseImmune responseMyD88-dependent innate immune responsesIL-1-dependent pathwayBone marrow chimeric miceProtective innate immune responseP. aeruginosaNovel transgenic mouse modelVentilator-associated pneumoniaIL-1R signalingTransgenic mouse modelP. aeruginosa infectionEpithelial cell responsesRadio-resistant cellsIntranasal infectionMyD88 expressionMultiple TLR pathwaysMyD88 functionAeruginosa infectionMouse modelTLR pathwayMurine infectionChimeric miceCell responsesInfection
2010
Recent advances in pulmonary fibrosis: implications for scleroderma
Homer RJ, Herzog EL. Recent advances in pulmonary fibrosis: implications for scleroderma. Current Opinion In Rheumatology 2010, 22: 683-689. PMID: 20693906, DOI: 10.1097/bor.0b013e32833ddcc9.BooksMeSH KeywordsAnimalsAutoantibodiesDisease Models, AnimalHumansIdiopathic Pulmonary FibrosisInflammationRespiratory MucosaScleroderma, SystemicConceptsPulmonary fibrosisEpithelial cell injuryCell injuryIdiopathic pulmonary fibrosisRole of lymphocytesAlternative macrophage activationPathogenesis of sclerodermaTranslational human studiesEpithelial-mesenchymal transitionEndoplasmic reticulum stressMost patientsSystemic sclerosisLung fibrosisLymphocyte functionEffective therapyLeading causeLung parenchymaFibrotic responseHuman studiesMacrophage activationScar tissueFibrosisPossible associationAnimal modelingPatients
2008
Acidic Mammalian Chitinase Is Secreted via an ADAM17/Epidermal Growth Factor Receptor-dependent Pathway and Stimulates Chemokine Production by Pulmonary Epithelial Cells*
Hartl D, He CH, Koller B, Da Silva CA, Homer R, Lee CG, Elias JA. Acidic Mammalian Chitinase Is Secreted via an ADAM17/Epidermal Growth Factor Receptor-dependent Pathway and Stimulates Chemokine Production by Pulmonary Epithelial Cells*. Journal Of Biological Chemistry 2008, 283: 33472-33482. PMID: 18824549, PMCID: PMC2586247, DOI: 10.1074/jbc.m805574200.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorLung epithelial cellsAcidic mammalian chitinaseChemokine productionEpithelial cellsT helper cell type 2 inflammationEpidermal growth factor receptor-dependent pathwayAsthma-like responsesType 2 inflammationMammalian chitinaseEpithelial cell productionReceptor-dependent pathwayPulmonary epithelial cellsEGFR-dependent pathwayGrowth factor receptorCotransfection experimentsEffector responsesParacrine fashionEGFR inhibitionSecretionFactor receptorA549 cellsAMCaseRecombinant AMCaseRegulatory effects
2007
Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma
Simeone-Penney MC, Severgnini M, Tu P, Homer RJ, Mariani TJ, Cohn L, Simon AR. Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma. The Journal Of Immunology 2007, 178: 6191-6199. PMID: 17475846, DOI: 10.4049/jimmunol.178.10.6191.Peer-Reviewed Original ResearchConceptsHouse dust miteAirway epitheliumAllergic inflammationRole of STAT3Murine modelNovel asthma therapiesSignificant decreaseSTAT3 activationTh2 cell recruitmentAcute phase responseWild-type animalsAirway hyperresponsivenessAirway eosinophiliaAirway inflammationAllergic asthmaAsthma therapyChronic asthmaLung inflammationC57BL/6 miceAllergic responsesDust miteEpithelial STAT3Immune cellsSmooth muscleSTAT3 transcription factor
2006
Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation
Homer RJ, Zhu Z, Cohn L, Lee CG, White WI, Chen S, Elias JA. Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2006, 291: l502-l511. PMID: 16556727, DOI: 10.1152/ajplung.00364.2005.Peer-Reviewed Original ResearchConceptsAirway epithelial cellsAllergic inflammationEpithelial cellsT-helper 2 inflammationClara cell secretory proteinProximal airway epithelial cellsDistal airway epitheliumMammalian chitinase familyMurine airway epithelial cellsIL-13 signalingProduction of mucusExpression of FOXA2Th1 inflammationTh2 inflammationDistal cellsAcidic mammalian chitinaseDistal airwaysPositive molecular markersAirway epitheliumInflammationAlveolar macrophagesProtein-expressing cellsMicrofilarial sheathMammalian chitinaseAMCase
2005
Role of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-γ-Induced Alveolar Remodeling and Pulmonary Emphysema
Zheng T, Kang MJ, Crothers K, Zhu Z, Liu W, Lee CG, Rabach LA, Chapman HA, Homer RJ, Aldous D, DeSanctis G, Underwood S, Graupe M, Flavell RA, Schmidt JA, Elias JA. Role of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-γ-Induced Alveolar Remodeling and Pulmonary Emphysema. The Journal Of Immunology 2005, 174: 8106-8115. PMID: 15944319, DOI: 10.4049/jimmunol.174.12.8106.Peer-Reviewed Original ResearchConceptsNull mutationEpithelial cell apoptosisCell apoptosisDNA injuryTissue remodelingProtease accumulationCaspase inhibitorsMitochondrial apoptosis pathway activationDeath receptorsPropidium iodide stainingCathepsin SHuman diseasesApoptosis responseApoptosis pathway activationApoptosis inhibitionCaspase-3ApoptosisIodide stainingPathway activationCathepsin S inhibitionMutationsRemodelingCritical eventsAlveolar remodelingIFN-gamma
2004
Acidic Mammalian Chitinase in Asthmatic Th2 Inflammation and IL-13 Pathway Activation
Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L, Hamid Q, Elias JA. Acidic Mammalian Chitinase in Asthmatic Th2 Inflammation and IL-13 Pathway Activation. Science 2004, 304: 1678-1682. PMID: 15192232, DOI: 10.1126/science.1095336.Peer-Reviewed Original ResearchConceptsTh2 inflammationAcidic mammalian chitinaseIL-13-induced responsesPathway activationTh2-dominated disordersMammalian chitinaseAirway hyperresponsivenessAsthma modelT helperHuman asthmaChemokine inductionInterleukin-13Exaggerated quantitiesImportant mediatorEpithelial cellsAsthmaInflammationActivationHyperresponsivenessInfectionActivation of the STAT pathway in acute lung injury
Severgnini M, Takahashi S, Rozo LM, Homer RJ, Kuhn C, Jhung JW, Perides G, Steer M, Hassoun PM, Fanburg BL, Cochran BH, Simon AR. Activation of the STAT pathway in acute lung injury. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2004, 286: l1282-l1292. PMID: 14729509, DOI: 10.1152/ajplung.00349.2003.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsCells, CulturedDisease Models, AnimalDNA-Binding ProteinsHydrochloric AcidInterleukin-6Janus Kinase 2KineticsLipopolysaccharidesLiverLungMaleMiceMice, Inbred BALB CMice, Inbred C57BLMitogen-Activated Protein KinasesOxidation-ReductionPancreatitisProtein-Tyrosine KinasesProto-Oncogene ProteinsRespiratory Distress SyndromeRespiratory MucosaSrc-Family KinasesSTAT3 Transcription FactorTrans-ActivatorsTumor Necrosis Factor-alphaConceptsAcute lung injuryIL-6Lung injuryLPS treatmentDevastating clinical problemGastric acid aspirationIntranasal LPS administrationResident lung cellsSTAT3 activationAcute pancreatitis modelSTAT activationAcid aspirationLPS administrationCytokine responsesInflammatory cellsInflammatory responsePancreatitis modelClinical problemMultiple organsLungLung cellsLPSEndothelial cellsTranscription factorsCritical mediator
2002
Interleukin-13 Mediates a Fundamental Pathway for Airway Epithelial Mucus Induced by CD4 T Cells and Interleukin-9
Whittaker L, Niu N, Temann U, Stoddard A, Flavell RA, Ray A, Homer RJ, Cohn L. Interleukin-13 Mediates a Fundamental Pathway for Airway Epithelial Mucus Induced by CD4 T Cells and Interleukin-9. American Journal Of Respiratory Cell And Molecular Biology 2002, 27: 593-602. PMID: 12397019, DOI: 10.1165/rcmb.4838.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCells, CulturedGene Expression RegulationInterferon-gammaInterleukin-13Interleukin-9LungMiceMice, Inbred BALB CMice, Mutant StrainsMice, TransgenicMucin 5ACMucinsNF-kappa BReceptors, InterferonReceptors, Interleukin-4Recombinant ProteinsRespiratory MucosaSignal TransductionTh2 CellsConceptsIL-13Th2 cellsTh2-induced airway inflammationEpithelial mucusCD4 Th cellsCD4 T cellsAbsence of interleukinIL-13 actsNuclear factor-kappaBAsthma resultsTh2 effectsAirway inflammationMucus hyperproductionNegative infectionsTh cytokinesInflammatory cellsRecipient miceTh cellsIL-4IL-5Respiratory tractAirway epitheliumIL-9T cellsComplete blockadeOverlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13–induced inflammation and remodeling
Lanone S, Zheng T, Zhu Z, Liu W, Lee CG, Ma B, Chen Q, Homer RJ, Wang J, Rabach LA, Rabach ME, Shipley JM, Shapiro SD, Senior RM, Elias JA. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13–induced inflammation and remodeling. Journal Of Clinical Investigation 2002, 110: 463-474. PMID: 12189240, PMCID: PMC150413, DOI: 10.1172/jci14136.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementChemotaxis, LeukocyteCytokinesEndopeptidasesFibrosisInflammationInterleukin-13LungLung ComplianceLung DiseasesMatrix Metalloproteinase 12Matrix Metalloproteinase 9MetalloendopeptidasesMiceMice, KnockoutMice, TransgenicPulmonary AlveoliRespiratory InsufficiencyRespiratory MucosaConceptsIL-13-induced inflammationMMP-9IL-13MMP-12MMP-2Respiratory failureAlveolar remodelingMatrix metalloproteinasesIL-13 transgenic miceMMP-12-deficient miceAccumulation of eosinophilsBronchoalveolar lavage fluidIL-13 actsIL-13 inductionMatrix metalloproteinases-9Recovery of leukocytesLung enlargementLymphocytic inflammationNeutrophil accumulationLymphocyte recoveryLavage fluidTotal leukocytesInflammatory effectsAlveolar enlargementMetalloproteinases-9IL-13-Induced Chemokine Responses in the Lung: Role of CCR2 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling
Zhu Z, Ma B, Zheng T, Homer RJ, Lee CG, Charo IF, Noble P, Elias JA. IL-13-Induced Chemokine Responses in the Lung: Role of CCR2 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling. The Journal Of Immunology 2002, 168: 2953-2962. PMID: 11884467, DOI: 10.4049/jimmunol.168.6.2953.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidCells, CulturedChemokine CCL2Chemokines, CCEndopeptidasesHyaluronic AcidInflammationInterleukin-13LungLung ComplianceMetaplasiaMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMinkMucusPhenotypeProtease InhibitorsPulmonary AlveoliPulmonary FibrosisReceptors, CCR2Receptors, ChemokineRespiratory InsufficiencyRespiratory MucosaRNA, MessengerTotal Lung CapacityTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsMonocyte chemotactic proteinTransgenic IL-13IL-13Potent stimulatorIL-13 transgenic miceIL-13-induced inflammationSecretory leukocyte proteinase inhibitorRole of CCR2Macrophage-derived chemokineActivation-regulated chemokineMacrophage inflammatory proteinHyaluronic acid accumulationPathogenesis of humanMucus metaplasiaCCR2 deficiencyRespiratory failureChemokine responsesPulmonary inflammationLung complianceMIP-2Lavage fluidMIP-1betaEotaxin-2MCP-1MIP-3alpha
2000
IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production
Wang J, Homer R, Hong L, Cohn L, Lee C, Jung S, Elias J. IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production. The Journal Of Immunology 2000, 165: 2222-2231. PMID: 10925310, DOI: 10.4049/jimmunol.165.4.2222.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAerosolsAllergensAnimalsBronchoalveolar Lavage FluidCytokinesGene Expression RegulationHumansImmunizationInterleukin-11MiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAMice, TransgenicMucinsMucusOvalbuminPulmonary EosinophiliaRecombinant ProteinsRespiratory MucosaSpecies SpecificityTh2 CellsTurkeysVascular Cell Adhesion Molecule-1ConceptsTh2 cell accumulationIL-11OVA challengeMucus hypersecretionIL-4IL-5VCAM-1Cell accumulationMucin 5AC (MUC5AC) gene expressionVCAM-1 gene expressionAg-specific IgEBronchoalveolar lavage (BAL) inflammationLung IL-4Th2 cytokine productionIFN-gamma productionEndothelial-cell VCAM-1IL-13 mRNAIL-13 proteinChemoattractant protein 2Chemoattractant protein-3Mucus metaplasiaTh1 inflammationPulmonary eosinophiliaTh2 inflammationAirway inflammation