2023
Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells.
Schupp J, Manning E, Chioccioli M, Kamp J, Christian L, Ryu C, Herzog E, Kühnel M, Prasse A, Kaminski N, Jonigk D, Homer R, Neubert L, Ius F, stringJustet A, Hariri L, Seeliger B, Welte T, Knipe R, Gottlieb J. Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 819-822. PMID: 37552025, PMCID: PMC10563189, DOI: 10.1164/rccm.202303-0544le.Peer-Reviewed Original Research
2015
Suppression of NLRX1 in chronic obstructive pulmonary disease
Kang MJ, Yoon CM, Kim BH, Lee CM, Zhou Y, Sauler M, Homer R, Dhamija A, Boffa D, West AP, Shadel GS, Ting JP, Tedrow JR, Kaminski N, Kim WJ, Lee CG, Oh YM, Elias JA. Suppression of NLRX1 in chronic obstructive pulmonary disease. Journal Of Clinical Investigation 2015, 125: 2458-2462. PMID: 25938787, PMCID: PMC4497738, DOI: 10.1172/jci71747.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCigarette smokeAlveolar destructionPulmonary diseaseHuman chronic obstructive pulmonary diseaseExpression of NLRX1Innate immune pathwaysInnate immune responseQuality of lifeCOPD patientsPulmonary functionSubsequent inflammationImmune responseInflammasome activationMurine modelIndependent cohortImmune pathwaysInflammationDisease severityInflammasome responseImportant mediatorCell apoptosisNLRX1Tissue effects
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 levelsSemaphorin 7A plays a critical role in TGF-β1–induced pulmonary fibrosis
Kang HR, Lee CG, Homer RJ, Elias JA. Semaphorin 7A plays a critical role in TGF-β1–induced pulmonary fibrosis. Journal Of Experimental Medicine 2007, 204: 1083-1093. PMID: 17485510, PMCID: PMC2118575, DOI: 10.1084/jem.20061273.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntigens, CDApoptosisCollagenDNA DamageImmunoblottingImmunohistochemistryIn Situ HybridizationIn Situ Nick-End LabelingIntegrin beta1MiceMice, TransgenicNerve Tissue ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPulmonary AlveoliPulmonary FibrosisReceptors, Cell SurfaceReverse Transcriptase Polymerase Chain ReactionSemaphorinsTransforming Growth Factor beta1ConceptsProtein kinase BSEMA 7APKB/Akt inhibitionAkt-dependent pathwayCritical roleSemaphorin 7ACCN proteinsFibroblast growth factor-2Kinase BCritical regulatorApoptosis regulatorMatrix proteinsGrowth factor 2Akt inhibitionBeta1 integrinReceptor componentsTissue remodelingFactor 2Fibrotic stimuliSmad 2/3Myofibroblast hyperplasiaGrowth factorRegulatorCentral roleProtein
2006
Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling
Shim YM, Zhu Z, Zheng T, Lee CG, Homer RJ, Ma B, Elias JA. Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling. The Journal Of Immunology 2006, 177: 1918-1924. PMID: 16849505, DOI: 10.4049/jimmunol.177.3.1918.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArachidonate 5-LipoxygenaseChronic DiseaseDinoprostoneInflammationInterleukin-13LeukotrienesLungMatrix Metalloproteinase 12MetalloendopeptidasesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPulmonary AlveoliPulmonary FibrosisSignal TransductionTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsIL-13-induced inflammationIL-13Transgenic IL-13Activation of TGFMatrix metalloproteinase-12Th2 inflammationPulmonary inflammationC57BL/6 miceChronic inflammationCysteinyl LTsFibrotic responseLevels of mRNATissue fibrosisLT metabolismInflammationAlveolar remodelingReceptor 1Metalloproteinase-12Pathway activationExaggerated levelsOptimal stimulationCytosolic phospholipasePathogenesisActivation pathwayRemodelingTransgenic 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 death
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 smokeRole 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-gammaIL-11 Receptor α in the Pathogenesis of IL-13-Induced Inflammation and Remodeling
Chen Q, Rabach L, Noble P, Zheng T, Lee CG, Homer RJ, Elias JA. IL-11 Receptor α in the Pathogenesis of IL-13-Induced Inflammation and Remodeling. The Journal Of Immunology 2005, 174: 2305-2313. PMID: 15699166, DOI: 10.4049/jimmunol.174.4.2305.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokines, CCFibroblastsHyaluronic AcidHyperoxiaInflammationInterleukin-11Interleukin-11 Receptor alpha SubunitInterleukin-13Interleukin-13 Receptor alpha1 SubunitLungMatrix MetalloproteinasesMetaplasiaMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMucinsProtein SubunitsPulmonary AlveoliPulmonary FibrosisReceptors, InterleukinReceptors, Interleukin-11Receptors, Interleukin-13Respiratory InsufficiencySignal TransductionTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsIL-13-induced inflammationIL-13IL-11IL-11RalphaIL-13-induced tissue responsesPotent stimulatorTransgenic IL-13Tissue effectsWild-type miceHyaluronic acid accumulationMucus metaplasiaTh2 inflammationRespiratory failureInflammatory disordersGob-5Major stimulatorCC chemokinesMyofibroblast accumulationInflammationTransgenic miceAlveolar remodelingReceptor αMatrix metalloproteinasesMiceDependent pathway
2004
The 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
2002
Overlapping 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-9Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure
Homer RJ, Zheng T, Chupp G, He S, Zhu Z, Chen Q, Ma B, Hite RD, Gobran LI, Rooney SA, Elias JA. Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2002, 283: l52-l59. PMID: 12060560, DOI: 10.1152/ajplung.00438.2001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAsthmaBronchoalveolar Lavage FluidGene ExpressionHypertrophyImmunohistochemistryInterleukin-13MiceMice, Inbred C57BLMice, Inbred CBAMice, TransgenicProteolipidsPulmonary AlveoliPulmonary FibrosisPulmonary Surfactant-Associated Protein APulmonary Surfactant-Associated ProteinsPulmonary SurfactantsRNA, MessengerConceptsType II cell hypertrophyIL-13Cell hypertrophyChronic pulmonary conditionsPathogenesis of asthmaBronchoalveolar lavage fluidTh2-mediated immunityIL-13 exposureProminent interstitial fibrosisWild-type miceAirway hyperresponsivenessMucus metaplasiaEosinophilic inflammationPulmonary diseaseInterstitial fibrosisLavage fluidPulmonary conditionsTwo- to threefold increaseSurfactant accumulationLittermate controlsPotent stimulatorSurfactant phospholipidsFibrosisKey mediatorHypertrophyIL-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
Airway Hyperresponsiveness and Airway Obstruction in Transgenic Mice
Kuhn C, Homer R, Zhu Z, Ward N, Flavell R, Geba G, Elias J. Airway Hyperresponsiveness and Airway Obstruction in Transgenic Mice. American Journal Of Respiratory Cell And Molecular Biology 2000, 22: 289-295. PMID: 10696065, DOI: 10.1165/ajrcmb.22.3.3690.Peer-Reviewed Original ResearchConceptsLittermate control miceTransgenic miceAirway obstructionControl miceIL-11Basal airway resistanceIL-6 (-/-) miceSubepithelial airway fibrosisObstructive lung diseasePathophysiology of asthmaAirway wall thicknessAirway fibrosisAirway hyperresponsivenessAirway reactivityMethacholine responsivenessAirway physiologyAirway responsesAirspace enlargementAirway resistanceCaliber changeIL-6Lung diseaseMononuclear cellsPulmonary disordersLuminal diameter
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