2007
IL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation
Kang MJ, Homer RJ, Gallo A, Lee CG, Crothers KA, Cho SJ, Rochester C, Cain H, Chupp G, Yoon HJ, Elias JA. IL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation. The Journal Of Immunology 2007, 178: 1948-1959. PMID: 17237446, DOI: 10.4049/jimmunol.178.3.1948.Peer-Reviewed Original ResearchConceptsChronic obstructive lung diseaseObstructive lung diseaseIL-18Wild-type miceCigarette smokeLung diseasePulmonary emphysemaIL-18RalphaPathogenesis of CSEffects of CSAir-exposed miceIL-18 pathwayIL-18 receptor αIL-18R signalingTh1 inflammationPulmonary macrophagesEpithelial apoptosisReceptor αInflammationPotent stimulatorEmphysemaCaspase-1MiceCritical roleElevated levelsTransforming 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
Transgenic 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 modelingInflammationRole 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
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 smokeIL-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
Pulmonary 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
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
2000
Inducible 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