2016
Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice
Sureshbabu A, Syed M, Das P, Janér C, Pryhuber G, Rahman A, Andersson S, Homer RJ, Bhandari V. Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice. American Journal Of Respiratory Cell And Molecular Biology 2016, 55: 722-735. PMID: 27374190, PMCID: PMC5105179, DOI: 10.1165/rcmb.2015-0349oc.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAdaptor Proteins, Signal TransducingAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisAutophagyBronchopulmonary DysplasiaCell LineFemaleHumansHyperoxiaHypertension, PulmonaryHypertrophy, Right VentricularInfant, NewbornLungMiceMicrotubule-Associated ProteinsNaphthyridinesPhenotypeRegulatory-Associated Protein of mTORTime FactorsTumor Suppressor Protein p53ConceptsAcute lung injuryBronchopulmonary dysplasiaLung injuryWild-type miceMechanistic targetRegulatory-Associated ProteinLysosomal-associated membrane protein 1Apoptotic cell deathFetal type II alveolar epithelial cellsMouse lungRole of autophagyHyperoxia-Induced Lung InjuryLight chain 3Activation of autophagyType II alveolar epithelial cellsRespiratory distress syndromeMembrane protein 1Developmental lung diseaseUseful therapeutic targetNeonatal mouse lungAlveolar epithelial cellsPharmacological inhibitorsTreatment of hyperoxiaCell deathAutophagic flux
2015
Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung
Sureshbabu A, Syed MA, Boddupalli CS, Dhodapkar MV, Homer RJ, Minoo P, Bhandari V. Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung. Respiratory Research 2015, 16: 4. PMID: 25591994, PMCID: PMC4307226, DOI: 10.1186/s12931-014-0162-6.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisDisease Models, AnimalGenotypeHumansHyperoxiaLungMice, Inbred C57BLMice, KnockoutMice, TransgenicPhenotypePneumoniaProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionTime FactorsTransforming Growth Factor beta1Up-RegulationConceptsImpaired alveolarizationBronchopulmonary dysplasiaAlveolar epithelial cellsPulmonary inflammationPulmonary phenotypeMouse lungAcute lung injuryType II alveolar epithelial cellsApoptotic cell deathCell deathNewborn mouse lungPotential therapeutic strategyGrowth factor betaNull mutant miceLung injuryImproved survivalNeonatal mortalityMonocyte infiltrationAbnormal alveolarizationAngiogenic mediatorsInflammatory signalsTGFβ1 expressionTherapeutic strategiesInflammatory macrophagesLung morphometry
2013
A Critical Regulatory Role for Macrophage Migration Inhibitory Factor in Hyperoxia-Induced Injury in the Developing Murine Lung
Sun H, Choo-Wing R, Sureshbabu A, Fan J, Leng L, Yu S, Jiang D, Noble P, Homer RJ, Bucala R, Bhandari V. A Critical Regulatory Role for Macrophage Migration Inhibitory Factor in Hyperoxia-Induced Injury in the Developing Murine Lung. PLOS ONE 2013, 8: e60560. PMID: 23637753, PMCID: PMC3639272, DOI: 10.1371/journal.pone.0060560.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietinsAnimalsBronchoalveolar LavageCell CountGene Expression RegulationGene Knockout TechniquesHyperoxiaInterleukin-6LungLung InjuryMacrophage Migration-Inhibitory FactorsMiceMice, TransgenicPhenotypeReceptor, TIE-2Receptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor AConceptsMIF knockoutHyperoxia exposureRoom airAngiopoietin-1Macrophage migration inhibitory factorHyperoxia-Induced InjuryAcute lung injuryProtein expressionRoom air controlsMigration inhibitory factorAngiopoietin-2 proteinTie-2 proteinMechanism of actionVascular mediatorsLung injuryControl lungsMIF mRNANewborn lungWT lungsNeonatal lungPostnatal dayMurine lungTransgenic miceLung morphometryCritical regulatory molecules
2012
Chronic inflammation and lung fibrosis: pleotropic syndromes but limited distinct phenotypes
Gifford AH, Matsuoka M, Ghoda LY, Homer RJ, Enelow RI. Chronic inflammation and lung fibrosis: pleotropic syndromes but limited distinct phenotypes. Mucosal Immunology 2012, 5: 480-484. PMID: 22806097, DOI: 10.1038/mi.2012.68.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisClinical entityHypersensitivity pneumonitisLung diseaseLung fibrosisDifferent clinical presentationsDistinct phenotypesPostinflammatory fibrosisClinical presentationRheumatoid arthritisChronic inflammationClinical syndromeTherapeutic responseClinical diseaseMultiple potential reasonsFibrosisFibrotic phenotypeExperimental modelDiseaseSyndromeMatrix depositionPhenotypePhenotypic distinctionPneumonitis
2011
A Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs
Harijith A, Choo-Wing R, Cataltepe S, Yasumatsu R, Aghai ZH, Janér J, Andersson S, Homer RJ, Bhandari V. A Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs. American Journal Of Respiratory Cell And Molecular Biology 2011, 44: 621-630. PMID: 21216975, PMCID: PMC3095982, DOI: 10.1165/rcmb.2010-0058oc.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaHuman bronchopulmonary dysplasiaLung architectureRole of IFNγMatrix metalloproteinase-9Caspase-3Final common pathwayMatrix metalloproteinases 2Downstream targetsImpaired alveolarizationLung injuryChemokine ligandMetalloproteinase-9IFNγ mRNAAngiopoietin-2Murine modelLittermate controlsPulmonary phenotypeMurine lungClinical relevanceLung phenotypeAngiopoietin-1IFNγMetalloproteinases 2Lung
2008
Endogenous IL-11 Signaling Is Essential in Th2- and IL-13–Induced Inflammation and Mucus Production
Lee CG, Hartl D, Matsuura H, Dunlop FM, Scotney PD, Fabri LJ, Nash AD, Chen NY, Tang CY, Chen Q, Homer RJ, Baca M, Elias JA. Endogenous IL-11 Signaling Is Essential in Th2- and IL-13–Induced Inflammation and Mucus Production. American Journal Of Respiratory Cell And Molecular Biology 2008, 39: 739-746. PMID: 18617680, PMCID: PMC2586049, DOI: 10.1165/rcmb.2008-0053oc.Peer-Reviewed Original ResearchConceptsIL-13 productionMucus productionIL-11Th2 inflammationIL-11RalphaAerosol antigen challengeAirway mucus productionBronchoalveolar lavage (BAL) inflammationPulmonary Th2 responsesLevels of IgEIL-13 responsesEndogenous IL-11Null mutant miceBAL inflammationMucus metaplasiaEosinophilic inflammationTh2 responsesAntigen challengeIL-11 receptorWT miceTh2 cytokinesIntraperitoneal administrationInflammationMucus responseMurine lung
2005
Role of CCR5 in IFN-γ–induced and cigarette smoke–induced emphysema
Ma B, Kang MJ, Lee CG, Chapoval S, Liu W, Chen Q, Coyle AJ, Lora JM, Picarella D, Homer RJ, Elias JA. Role of CCR5 in IFN-γ–induced and cigarette smoke–induced emphysema. Journal Of Clinical Investigation 2005, 115: 3460-3472. PMID: 16284650, PMCID: PMC1280966, DOI: 10.1172/jci24858.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnnexin A5ApoptosisBronchoalveolar LavageCell DeathChemokinesDNADNA PrimersEmphysemaEnzyme-Linked Immunosorbent AssayFemaleImmunohistochemistryIn Situ Nick-End LabelingInflammationInterferon-gammaLigandsLungMacrophagesMatrix Metalloproteinase 9MiceMice, Inbred C57BLMice, TransgenicMutationPhenotypePulmonary AlveoliReceptors, CCR5Reverse Transcriptase Polymerase Chain ReactionRNA, MessengerSmokingTime FactorsConceptsCCR5 ligandsIFN-gammaPotent stimulatorCigarette smoke-induced inflammationCigarette smoke-induced emphysemaSecretory leukocyte protease inhibitorImportance of CCR5Murine emphysema modelPathogenesis of IFNRANTES/CCLSmoke-induced inflammationDNA injuryRole of CCR5Smoke-induced emphysemaLeukocyte protease inhibitorSelect chemokinesTh1 inflammationPulmonary inflammationEmphysema modelCXC chemokinesTissue destructionIFN-gamma stimulationMMP-9CCR5Cigarette smoke
2002
Transgenic Overexpression of Interleukin (IL)-10 in the Lung Causes Mucus Metaplasia, Tissue Inflammation, and Airway Remodeling via IL-13-dependent and -independent Pathways*
Lee CG, Homer RJ, Cohn L, Link H, Jung S, Craft JE, Graham BS, Johnson TR, Elias JA. Transgenic Overexpression of Interleukin (IL)-10 in the Lung Causes Mucus Metaplasia, Tissue Inflammation, and Airway Remodeling via IL-13-dependent and -independent Pathways*. Journal Of Biological Chemistry 2002, 277: 35466-35474. PMID: 12107190, DOI: 10.1074/jbc.m206395200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceChloride ChannelsCloning, MolecularDNA PrimersFluorescent Antibody TechniqueGene Expression RegulationIn Situ HybridizationInflammationInterleukin-10Interleukin-13LungMiceMice, TransgenicMolecular Sequence DataMucoproteinsMucous MembranePhenotypePolymerase Chain ReactionReceptors, Interleukin-4STAT6 Transcription FactorTrans-ActivatorsConceptsMucus metaplasiaIL-10Tissue inflammationIL-13Tumor necrosis factor productionIL-13/ILLipopolysaccharide-induced inflammationNecrosis factor productionAirway fibrosisNeutrophil accumulationAirway remodelingSubepithelial fibrosisGob-5Levels of mRNAMetaplasiaInflammationTransgenic miceFibrosisSTAT-6Effector propertiesTransgenic overexpressionFactor productionMiceInterleukinMultiple mechanismsIL-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
2001
Airway Inflammation and Remodeling in Asthma
ZHU Z, LEE C, ZHENG T, CHUPP G, WANG J, HOMER R, NOBLE P, HAMID Q, ELIAS J. Airway Inflammation and Remodeling in Asthma. American Journal Of Respiratory And Critical Care Medicine 2001, 164: s67-s70. PMID: 11734470, DOI: 10.1164/ajrccm.164.supplement_2.2106070.Peer-Reviewed Original ResearchConceptsAirway fibrosisAsthmatic airwaysIL-11IL-13Asthma-like inflammationExaggerated cytokine productionImportance of airwayMucin gene expressionHyaluronic acid accumulationAirway healingAsthmatic tissuesSevere airwayAirway inflammationAirway remodelingAsthmatic subjectsSubepithelial fibrosisAsthma phenotypesCytokine productionMurine airwaysMucous metaplasiaAirwayTransgenic miceNatural historyInterleukin-11FibrosisUse of the Tetracycline-controlled Transcriptional Silencer (tTS) to Eliminate Transgene Leak in Inducible Overexpression Transgenic Mice*
Zhu Z, Ma B, Homer R, Zheng T, Elias J. Use of the Tetracycline-controlled Transcriptional Silencer (tTS) to Eliminate Transgene Leak in Inducible Overexpression Transgenic Mice*. Journal Of Biological Chemistry 2001, 276: 25222-25229. PMID: 11331286, DOI: 10.1074/jbc.m101512200.Peer-Reviewed Original ResearchConceptsIL-13Reverse tetracycline transactivatorIL-13 productionTetracycline-controlled transcriptional silencerOverexpression transgenic miceTransgene expressionMucus metaplasiaLung volumeAlveolar enlargementDOX administrationDoxycycline administrationTransgenic miceParental miceMiceCC10 promoterDoxycyclineTetracycline transactivatorBase lineAdministrationPhenotypeVivo
1997
Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.
Ray P, Tang W, Wang P, Homer R, Kuhn C, Flavell RA, Elias JA. Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes. Journal Of Clinical Investigation 1997, 100: 2501-2511. PMID: 9366564, PMCID: PMC508450, DOI: 10.1172/jci119792.Peer-Reviewed Original Research