2016
Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis
Peng X, Moore M, Mathur A, Zhou Y, Sun H, Gan Y, Herazo‐Maya J, Kaminski N, Hu X, Pan H, Ryu C, Osafo‐Addo A, Homer RJ, Feghali‐Bostwick C, Fares W, Gulati M, Hu B, Lee C, Elias JA, Herzog EL. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. The FASEB Journal 2016, 30: 4056-4070. PMID: 27609773, PMCID: PMC5102121, DOI: 10.1096/fj.201600373r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalHumansLungMacrophagesMice, KnockoutNerve Tissue ProteinsPulmonary FibrosisReceptors, Cell SurfaceReceptors, VirusSynaptotagminsTransforming Growth Factor beta1ConceptsLung fibrosisPlexin C1Macrophage migrationPulmonary fibrosisBone marrow-derived cellsSynaptotagmin-7Idiopathic pulmonary fibrosisInterstitial lung diseaseMarrow-derived cellsTGF-β1 overexpressionFatal conditionLung diseaseMonocyte migrationUnrecognized observationCollagen accumulationFibrosisMice showBoyden chamberGenetic deletionLungMouse macrophagesSemaphorin receptorsMacrophagesC1s deficiencyDeficiency
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
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
Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease
Gan Y, Reilkoff R, Peng X, Russell T, Chen Q, Mathai SK, Homer R, Gulati M, Siner J, Elias J, Bucala R, Herzog E. Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease. Arthritis & Rheumatism 2011, 63: 2484-2494. PMID: 21484765, PMCID: PMC3651701, DOI: 10.1002/art.30386.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsDisease Models, AnimalFibroblastsHumansIntegrin beta1Lung Diseases, InterstitialMiceMice, KnockoutPulmonary FibrosisScleroderma, SystemicSemaphorinsSignal TransductionTransforming Growth Factor beta1ConceptsPeripheral blood mononuclear cellsInterstitial lung diseaseBone marrow-derived cellsMarrow-derived cellsSemaphorin 7AGrowth factor-β1Lung diseaseLung fibrosisFactor-β1Human peripheral blood mononuclear cellsNormal human peripheral blood mononuclear cellsSemaphorin 7a expressionBone marrow transplantationBlood mononuclear cellsReceptor β1 integrinΒ1 integrinFibrocyte differentiationMarrow transplantationPulmonary fibrosisMononuclear cellsProfibrotic effectsTGFβ1 geneMurine modelFibrosisTissue accumulation
2007
P21 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 inhibitorsSemaphorin 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 roleProteinA Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract
Niu N, Le Goff MK, Li F, Rahman M, Homer RJ, Cohn L. A Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract. The Journal Of Immunology 2007, 178: 3846-3855. PMID: 17339484, DOI: 10.4049/jimmunol.178.6.3846.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAsthmaChronic DiseaseDisease Models, AnimalEosinophiliaImmune ToleranceInflammationMacrophagesMiceMice, Inbred BALB CMice, TransgenicTh1 CellsTh2 CellsTransforming Growth Factor beta1ConceptsAirway inflammationInflammatory diseasesRespiratory tractTh2-induced airway inflammationChronic airway inflammatory diseaseLymphocyte-deficient miceState of immunosuppressionAcute airway inflammationAirway inflammatory diseasesEffector Th cellsTh2 cells resultsAirway hyperresponsivenessInflammation wanesTh2 modelEffector Th1Respiratory illnessTh cellsInhalational exposureInflammationInhibitory effectSuch diseasesDiseaseStriking inhibitionTh1Localized treatmentTransforming Growth Factor (TGF)-β1 Stimulates Pulmonary Fibrosis and Inflammation via a Bax-dependent, Bid-activated Pathway That Involves Matrix Metalloproteinase-12*
Kang HR, Cho SJ, Lee CG, Homer RJ, Elias JA. Transforming Growth Factor (TGF)-β1 Stimulates Pulmonary Fibrosis and Inflammation via a Bax-dependent, Bid-activated Pathway That Involves Matrix Metalloproteinase-12*. Journal Of Biological Chemistry 2007, 282: 7723-7732. PMID: 17209037, DOI: 10.1074/jbc.m610764200.Peer-Reviewed Original ResearchConceptsMMP-12Pulmonary fibrosisWild typeGrowth factorInterstitial lung diseaseEffects of TGFMatrix metalloproteinase-12Pulmonary diseaseExaggerated productionPulmonary responseLung diseaseMMP-9Effector functionsTIMP-1Matrix metalloproteinaseFibrosisPotent stimulatorMetalloproteinase-12TGFBax activationInflammationPathogenesisBaxApoptosisDisease
2006
Genetic Control of Transforming Growth Factor-β1–induced Emphysema and Fibrosis in the Murine Lung
Lee CG, Cho S, Homer RJ, Elias JA. Genetic Control of Transforming Growth Factor-β1–induced Emphysema and Fibrosis in the Murine Lung. Annals Of The American Thoracic Society 2006, 3: 476a-477. PMID: 16921114, DOI: 10.1513/pats.200603-040ms.Peer-Reviewed Original ResearchAnimalsDisease Models, AnimalDNAGene ExpressionMiceMice, Inbred BALB CMice, Inbred C57BLPulmonary EmphysemaPulmonary FibrosisTransforming Growth Factor beta1Role 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 ResearchMeSH KeywordsAnimalsApoptosisDNAGene ExpressionHumansPulmonary AlveoliPulmonary FibrosisTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsTissue 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 ResearchMeSH KeywordsAdenosineAnimalsEmphysemaFemaleFibrosisInflammationInterleukin-4MaleMiceMice, Inbred BALB CMice, Inbred C57BLPulmonary AlveoliRatsSpecies SpecificityTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsIL-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 Early Growth Response-1 (Egr-1) in Interleukin-13-induced Inflammation and Remodeling*
Cho SJ, Kang MJ, Homer RJ, Kang HR, Zhang X, Lee PJ, Elias JA, Lee CG. Role of Early Growth Response-1 (Egr-1) in Interleukin-13-induced Inflammation and Remodeling*. Journal Of Biological Chemistry 2006, 281: 8161-8168. PMID: 16439363, DOI: 10.1074/jbc.m506770200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar LavageCaspasesCell DeathCollagenDNAEarly Growth Response Protein 1Enzyme InhibitorsFibrosisFlavonoidsImmunoblottingIn Situ Nick-End LabelingInflammationInterleukin-13LungMatrix Metalloproteinase 9MiceMice, Inbred C57BLMice, TransgenicMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Models, BiologicalModels, StatisticalRNARNA, MessengerSTAT6 Transcription FactorTh2 CellsTime FactorsTransforming Growth Factor betaTransforming Growth Factor beta1TransgenesConceptsIL-13Early growth response 1IL-13-induced tissue responsesEgr-1Transgenic IL-13Matrix metalloproteinase-9Wild-type miceResponse 1Th2 inflammationCXC chemokinesMetalloproteinase-9Type miceMetalloproteinase-1Transgenic miceAlveolar remodelingTissue inhibitorInflammationPotent stimulatorImportant stimulatorMiceTissue effectsKey roleTissue responsePathogenesisApoptosis regulator
2005
IL-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
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 1
2002
IL-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
Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor β1
Lee C, Homer R, Zhu Z, Lanone S, Wang X, Koteliansky V, Shipley J, Gotwals P, Noble P, Chen Q, Senior R, Elias J. Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor β1. Journal Of Experimental Medicine 2001, 194: 809-822. PMID: 11560996, PMCID: PMC2195954, DOI: 10.1084/jem.194.6.809.Peer-Reviewed Original ResearchConceptsIL-13Fibrogenic effectsT helper cell type 2 inflammationTissue fibrosisIL-13 overexpressionMMP-9 null miceType 2 inflammationTransforming Growth Factor-β1Wild-type miceGrowth factor-β1Pulmonary fibrosisTGF-beta pathwayFactor-β1Matrix metalloproteinasePotent stimulatorFibrosisNull miceTGFPlasminogen activatorDecreased levelsKey mediatorMiceGrowth factorUrinary plasminogen activatorProtein 1