2021
Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma
Robles-Oteiza C, Ayeni D, Levy S, Homer RJ, Kaech SM, Politi K. Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma. Disease Models & Mechanisms 2021, 14: dmm049072. PMID: 34494649, PMCID: PMC8617309, DOI: 10.1242/dmm.049072.Peer-Reviewed Original ResearchConceptsHuman diphtheria toxin receptorDiphtheria toxin receptorTumor regressionEGFR-mutant lung cancerEGFR-mutant lung adenocarcinomaEGFR-mutant tumorsMutant EGFRTissue-specific promotorsFVB miceLung cancerSystemic administrationLung adenocarcinomaMurine lungRapid regressionConditional ablationTumor cellsUpregulated expressionMiceElevated expressionToxin receptorHB-EGFCell populationsHBEGFEGFRPrimary target
2013
Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway
Choo-Wing R, Syed MA, Harijith A, Bowen B, Pryhuber G, Janér C, Andersson S, Homer RJ, Bhandari V. Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway. American Journal Of Respiratory Cell And Molecular Biology 2013, 48: 749-757. PMID: 23470621, PMCID: PMC3727872, DOI: 10.1165/rcmb.2012-0381oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBronchopulmonary DysplasiaCelecoxibCell DeathCyclooxygenase 2Cyclooxygenase 2 InhibitorsEndoplasmic Reticulum StressHumansHyperoxiaImmunohistochemistryInfant, NewbornInterferon-gammaLungMiceMice, Inbred C57BLMice, TransgenicPyrazolesRNA, Small InterferingSulfonamidesTranscription Factor CHOPConceptsBronchopulmonary dysplasiaCyclooxygenase-2Endoplasmic reticulum stress-dependent pathwaysER stress pathway activationPathway mediatorsHuman bronchopulmonary dysplasiaFinal common pathwayAlveolar epithelial cellsImpaired alveolarizationStress pathway activationCOX2 inhibitionMurine modelMurine lungClinical relevanceIFNVivo modelHyperoxiaLungHuman lungPathway activationCHOP siRNAStress-dependent pathwaysInjuryEpithelial cellsCommon pathwayA 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
Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis
Reilkoff RA, Peng H, Murray LA, Peng X, Russell T, Montgomery R, Feghali-Bostwick C, Shaw A, Homer RJ, Gulati M, Mathur A, Elias JA, Herzog EL. Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2012, 187: 180-188. PMID: 23220917, PMCID: PMC3570653, DOI: 10.1164/rccm.201206-1109oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisRegulatory T cellsProgressive idiopathic pulmonary fibrosisSEMA 7ATGF-β1Pulmonary fibrosisLung fibrosisT cellsMurine lungIL-10Bone marrow-derived cellsAdoptive transfer approachT-cell mediatorsMarrow-derived cellsTransforming Growth Factor-β1Murine lung fibrosisGrowth factor-β1Lung CD4Adoptive transferIL-17AIL-4Disease progressionSemaphorin 7ACD4Mouse model
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 lungDevelopmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung
Bhandari V, Choo-Wing R, Lee CG, Yusuf K, Nedrelow JH, Ambalavanan N, Malkus H, Homer RJ, Elias JA. Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung. American Journal Of Respiratory Cell And Molecular Biology 2008, 39: 420-430. PMID: 18441284, PMCID: PMC2551703, DOI: 10.1165/rcmb.2007-0024oc.Peer-Reviewed Original ResearchMeSH KeywordsAmniotic FluidAnimalsAnimals, NewbornBronchopulmonary DysplasiaCapillary PermeabilityFemaleHemorrhageHumansHyperoxiaInfant, NewbornLungLung DiseasesMiceMice, TransgenicNitric OxidePregnancyPulmonary SurfactantsRespiratory Distress Syndrome, NewbornTracheaVascular Endothelial Growth Factor AConceptsVascular endothelial growth factorVEGF levelsLung developmentNitric oxide mediationNO-dependent mechanismAdult murine lungPotential clinical benefitTransgenic murine modelSignificant differencesEndothelial growth factorBronchopulmonary dysplasiaLung injuryPulmonary hemorrhageCytokine responsesClinical benefitNeonatal lungHuman neonatesMurine modelMurine lungMature lungLungPathologic conditionsAdult lungSurfactant phospholipidsExtravascular effectsIL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung
Zheng T, Liu W, Oh SY, Zhu Z, Hu B, Homer RJ, Cohn L, Grusby MJ, Elias JA. IL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung. The Journal Of Immunology 2008, 180: 522-529. PMID: 18097054, DOI: 10.4049/jimmunol.180.1.522.Peer-Reviewed Original ResearchConceptsIL-13Ralpha2Pulmonary inflammationIL-13Inflammatory responseMurine lungHigh-affinity IL-13 receptorsTransgenic IL-13IL-13 receptor α2Production of chemokinesEnhanced inflammatory responseIL-13 receptorMucus metaplasiaTh2 inflammationAirway remodelingSubepithelial fibrosisIL-4Receptor α2Critical cytokineIL-13Ralpha1IL-4RalphaDecoy receptorPhysiologic responsesInflammationTissue effectsReceptors
2007
Inhibition of NF-κB Activation Reduces the Tissue Effects of Transgenic IL-13
Chapoval SP, Al-Garawi A, Lora JM, Strickland I, Ma B, Lee PJ, Homer RJ, Ghosh S, Coyle AJ, Elias JA. Inhibition of NF-κB Activation Reduces the Tissue Effects of Transgenic IL-13. The Journal Of Immunology 2007, 179: 7030-7041. PMID: 17982094, DOI: 10.4049/jimmunol.179.10.7030.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsApoptosisCaspasesHeterocyclic Compounds, 3-RingI-kappa B KinaseInflammationInhibitor of Apoptosis ProteinsInterleukin-13MiceMice, Mutant StrainsMice, TransgenicMucusNF-kappa B p50 SubunitPeptidesPulmonary AlveoliPulmonary FibrosisPyridinesReceptors, Cell SurfaceRespiratory HypersensitivitySignal TransductionTh2 CellsConceptsTransgenic IL-13IL-13Alveolar remodelingIL-13 transgenic miceNF-kappaBMajor Th2 cytokinesExcessive mucus productionTissue effectsNF-κB activationNF-kappaB activationNF-kappaB activityNF-kappaB componentsAirway hyperresponsivenessTh2 cytokinesTissue inflammationPharmacologic approachesMucus productionIL-13Ralpha1Murine lungSmall molecule inhibitorsTissue alterationsNF-kappaB.MiceCell apoptosisDiminished levelsP21 Regulates TGF-β1–Induced Pulmonary Responses via a TNF-α–Signaling Pathway
Yamasaki M, Kang HR, Homer RJ, Chapoval SP, Cho SJ, Lee BJ, Elias JA, Lee CG. P21 Regulates TGF-β1–Induced Pulmonary Responses via a TNF-α–Signaling Pathway. American Journal Of Respiratory Cell And Molecular Biology 2007, 38: 346-353. PMID: 17932374, PMCID: PMC2258454, DOI: 10.1165/rcmb.2007-0276oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCrosses, GeneticCyclin-Dependent Kinase Inhibitor p21DoxycyclineFibrosisImmunohistochemistryInflammationLungMiceMice, Inbred C57BLMice, TransgenicRandom AllocationRNA, MessengerSignal TransductionStatistics as TopicTransforming Growth Factor beta1Tumor Necrosis Factor-alphaConceptsMurine lungCyclin-dependent kinase inhibitorAbsence of p21Caspase-3 activationP21 locusKey regulatorTNF-alpha expressionEffects of TGFExpression of p21Negative modulatorAlveolar destructionLung inflammationTransgenic overexpressionParenchymal destructionPulmonary responseApoptosisRepair responseP21 expressionRegulatory cytokinesMyofibroblast accumulationP21TGF-β1Epithelial cellsEpithelial apoptosisKinase inhibitors
2006
State of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease
Elias JA, Kang MJ, Crothers K, Homer R, Lee CG. State of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease. Annals Of The American Thoracic Society 2006, 3: 494-498. PMID: 16921126, DOI: 10.1513/pats.200603-068ms.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseVascular endothelial growth factorSecretory leukocyte proteinase inhibitorTh1/Tc1Obstructive pulmonary diseaseAlveolar destructionIFN-gammaMatrix metalloproteinasesMucus metaplasiaPulmonary diseaseCCR5-dependent mechanismEmphysematous alveolar destructionCigarette smoke exposureCytokine IFN-gammaIFN-gamma responsesEndothelial growth factorApoptosis-independent pathwayCCR5/Pulmonary fibrosisPulmonary responseSmoke exposureIL-13CC chemokinesFibrotic responseMurine lungTransgenic Modeling of Transforming Growth Factor-β1
Lee CG, Kang HR, Homer RJ, Chupp G, Elias JA. Transgenic Modeling of Transforming Growth Factor-β1. Annals Of The American Thoracic Society 2006, 3: 418-423. PMID: 16799085, PMCID: PMC2658706, DOI: 10.1513/pats.200602-017aw.Peer-Reviewed Original ResearchConceptsTissue fibrosisMucus metaplasiaIL-13Alveolar remodelingSpecific chemokine receptorsTransforming Growth Factor-β1Vascular endothelial growth factorGrowth factor-β1Endothelial growth factorEosinophilic inflammationTh2 responsesVascular responsesChemokine receptorsCC chemokinesPathologic fibrosisMurine lungEpithelial apoptosisFactor-β1Transgenic miceFibrosisPotent stimulatorAdenosine metabolismIL-11Transgenic modelingInflammationAdenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis
Ma B, Blackburn MR, Lee CG, Homer RJ, Liu W, Flavell RA, Boyden L, Lifton RP, Sun CX, Young HW, Elias JA. Adenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis. Journal Of Clinical Investigation 2006, 116: 1274-1283. PMID: 16670768, PMCID: PMC1451205, DOI: 10.1172/jci26372.Peer-Reviewed Original ResearchConceptsIL-4C57BL/6 miceBALB/cAirway fibrosisEosinophilic inflammationAdenosine metabolismEmphysematous alveolar destructionTissue adenosine levelsAdenosine receptor expressionIL-4 inducesAdenosine deaminase activityAlveolar destructionTh1 cytokinesC57BL/6 animalsEmphysematous destructionAdenosine levelsReceptor expressionTg animalsMurine lungMetalloproteinase-2Alveolar remodelingTissue inhibitorFibrosisInflammationPremature deathRole of CCR5 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling
Ma B, Liu W, Homer RJ, Lee PJ, Coyle AJ, Lora JM, Lee CG, Elias JA. Role of CCR5 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling. The Journal Of Immunology 2006, 176: 4968-4978. PMID: 16585593, DOI: 10.4049/jimmunol.176.8.4968.Peer-Reviewed Original ResearchConceptsIL-13-induced inflammationIL-13IL-13-induced tissue responsesMIP-1alpha/CCL3IL-13 inhibitionTransgenic IL-13Expression of CCR5Role of CCR5Tissue remodelingMatrix metalloproteinase-9MIP-1beta/CCL4CCR5 chemokine receptorInflammatory cell apoptosisIL-13 stimulationSelect chemokinesTh2 inflammationRespiratory failureCCR5 expressionChemokine receptorsMetalloproteinase-9Murine lungCCR5Alveolar remodelingCCR5 inductionInflammation
2004
Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis
Lee CG, Cho SJ, Kang MJ, Chapoval SP, Lee PJ, Noble PW, Yehualaeshet T, Lu B, Flavell RA, Milbrandt J, Homer RJ, Elias JA. Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis. Journal Of Experimental Medicine 2004, 200: 377-389. PMID: 15289506, PMCID: PMC2211975, DOI: 10.1084/jem.20040104.Peer-Reviewed Original ResearchConceptsVivo effector functionGrowth factor-β1Early growth response gene-1Pulmonary fibrosisSeptal rupturePulmonary disordersInterstitial diseaseEffector functionsFibrotic responseMurine lungTissue fibrosisEpithelial apoptosisFactor-β1Alveolar remodelingResponse gene-1FibrosisBioactive TGFTGFMyocyte hyperplasiaGrowth factorEarly growth response geneApoptosisLungPathogenesisGene 1The C10/CCL6 Chemokine and CCR1 Play Critical Roles in the Pathogenesis of IL-13-Induced Inflammation and Remodeling
Ma B, Zhu Z, Homer RJ, Gerard C, Strieter R, Elias JA. The C10/CCL6 Chemokine and CCR1 Play Critical Roles in the Pathogenesis of IL-13-Induced Inflammation and Remodeling. The Journal Of Immunology 2004, 172: 1872-1881. PMID: 14734772, DOI: 10.4049/jimmunol.172.3.1872.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCathepsinsChemokine CCL2Chemokines, CCDown-RegulationImmune SeraInflammationInterleukin-13LungLung ComplianceLung Volume MeasurementsMatrix Metalloproteinase 2Matrix Metalloproteinase 9MiceMice, Inbred C57BLMice, KnockoutMice, TransgenicProtease InhibitorsPulmonary AlveoliReceptors, CCR1Receptors, ChemokineUp-RegulationConceptsIL-13-induced inflammationMatrix metalloproteinase-2IL-13Potent stimulatorMMP-9Alveolar remodelingMonocyte chemoattractant protein-1Transgenic IL-13Inflammatory protein-1alphaChemoattractant protein-1Wild-type miceIL-13 stimulationPulmonary phenotypeLevels of mRNAMetalloproteinase-4Murine lungMetalloproteinase-2Tissue inhibitorInflammationTargeted null mutationCompliance alterationsPathogenesisCCL6ChemokinesProtein 1
2000
Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung
Wang Z, Zheng T, Zhu Z, Homer R, Riese R, Chapman H, Shapiro S, Elias J. Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung. Journal Of Experimental Medicine 2000, 192: 1587-1600. PMID: 11104801, PMCID: PMC2193095, DOI: 10.1084/jem.192.11.1587.Peer-Reviewed Original ResearchConceptsAdult murine lungMurine lungProtease/antiprotease balanceChronic obstructive pulmonary diseaseSecretory leukocyte proteinase inhibitorNeutrophil-rich inflammationObstructive pulmonary diseaseInterferon γ inductionPulmonary diseasePulmonary complianceChronic inflammationInflammatory responseLung volumePulmonary emphysemaPulmonary tissueΓ inductionAlveolar enlargementMMP-9Matrix metalloproteinaseEmphysemaLungInflammationSelective inhibitionProminent proteaseMacrophagesInducible targeting of IL-13 to the adult lung causes matrix metalloproteinase– and cathepsin-dependent emphysema
Zheng T, Zhu Z, Wang Z, Homer R, Ma B, Riese R, Chapman H, Shapiro S, Elias J. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase– and cathepsin-dependent emphysema. Journal Of Clinical Investigation 2000, 106: 1081-1093. PMID: 11067861, PMCID: PMC301418, DOI: 10.1172/jci10458.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseCigarette smoke exposureIL-13Smoke exposureSignificant chronic obstructive pulmonary diseaseObstructive pulmonary diseaseAdult murine lungMinority of smokersVaried natural historyAirway hyperresponsivenessMucus metaplasiaLung functionPulmonary diseasePulmonary inflammationLung volumeCritical cytokineMurine lungMMP-2Matrix metalloproteinaseInflammationPotent stimulatorEmphysemaAdult lungLungNatural history