2016
SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis
Tzouvelekis A, Yu G, Lino Cardenas CL, Herazo-Maya JD, Wang R, Woolard T, Zhang Y, Sakamoto K, Lee H, Yi JS, DeIuliis G, Xylourgidis N, Ahangari F, Lee PJ, Aidinis V, Herzog EL, Homer R, Bennett AM, Kaminski N. SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2016, 195: 500-514. PMID: 27736153, PMCID: PMC5378419, DOI: 10.1164/rccm.201602-0329oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisProfibrotic stimuliLung fibroblastsChronic fatal lung diseaseMyofibroblast differentiationPrimary human lung fibroblastsFatal lung diseaseNovel therapeutic strategiesVivo therapeutic effectPotential therapeutic usefulnessHuman lung fibroblastsMouse lung fibroblastsDismal prognosisFibroblastic fociLung fibrosisLung diseaseBleomycin modelTherapeutic effectTherapeutic usefulnessTherapeutic strategiesTherapeutic targetTransgenic miceFibrosisSHP2 overexpressionMatrix Metalloproteinase–Targeted Imaging of Lung Inflammation and Remodeling
Golestani R, Razavian M, Ye Y, Zhang J, Jung JJ, Toczek J, Gona K, Kim HY, Elias JA, Lee CG, Homer RJ, Sadeghi MM. Matrix Metalloproteinase–Targeted Imaging of Lung Inflammation and Remodeling. Journal Of Nuclear Medicine 2016, 58: 138-143. PMID: 27469361, PMCID: PMC5209638, DOI: 10.2967/jnumed.116.176198.Peer-Reviewed Original ResearchConceptsSmall-animal SPECT/CTSPECT/CTMatrix metalloproteinasesTg lungsLung inflammationTg miceIL-13 transgenic miceReal-time reverse transcription-polymerase chain reactionReverse transcription-polymerase chain reactionWild-type littermatesTranscription-polymerase chain reactionWild-type animalsMolecular imagingPulmonary inflammationPulmonary diseaseCD68 expressionLung diseasePolymerase chain reactionPulmonary pathologyEarly diagnosisInflammationMMP-13Transgenic miceMatrix metalloproteinaseMMP-12
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
2010
Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation
Wright PL, Yu J, Di YP, Homer RJ, Chupp G, Elias JA, Cohn L, Sessa WC. Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation. Journal Of Experimental Medicine 2010, 207: 2595-2607. PMID: 20975041, PMCID: PMC2989775, DOI: 10.1084/jem.20100786.Peer-Reviewed Original ResearchConceptsLung inflammationTh2-mediated lung inflammationSevere human asthmaAsthma-like phenotypeNonallergic miceHuman asthmaInflammation resultsKO miceLung tissueNogo expressionAirway epitheliumSmooth muscleReticulon 4BTransgenic miceLung epitheliumEpithelial reconstitutionMiceMarked reductionProtective genesEndogenous regulatorNogoInflammationLungPLUNCTransgenic expression
2009
Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13–induced tissue responses and apoptosis
Lee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, Sohn MH, Cohn L, Homer RJ, Kozhich AA, Humbles A, Kearley J, Coyle A, Chupp G, Reed J, Flavell RA, Elias JA. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13–induced tissue responses and apoptosis. Journal Of Experimental Medicine 2009, 206: 1149-1166. PMID: 19414556, PMCID: PMC2715037, DOI: 10.1084/jem.20081271.Peer-Reviewed Original ResearchConceptsBRP-39/YKLBreast regression protein 39YKL-40BRP-39Th2 responsesIL-13-induced tissue responsesDendritic cell accumulationAlternative macrophage activationApoptosis/cell deathProtein 39Protein kinase B/AktTh2 inflammationDisease activityAntigen sensitizationEffector phaseTissue inflammationExaggerated quantitiesPulmonary epitheliumTherapeutic targetMacrophage activationTransgenic miceCell accumulationFas expressionNovel regulatory roleMice
2007
Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia
Choo-Wing R, Nedrelow JH, Homer RJ, Elias JA, Bhandari V. Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2007, 293: l142-l150. PMID: 17400600, DOI: 10.1152/ajplung.00434.2006.Peer-Reviewed Original ResearchConceptsIL-13 transgenic miceIL-6Transgenic miceTracheal aspirate levelsWild-type littermate controlsIL-6 levelsRespiratory distress syndromeAngiogenic factor expressionLung injuryDistress syndromePremature neonatesTracheal aspiratesAdverse outcomesIL-13Human neonatesProtective effectSurvival advantageLittermate controlsAdult miceClinical relevanceTUNEL stainingCytoprotective effectsNewborn animalsMature miceFactor expression
2006
IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells
Temann UA, Laouar Y, Eynon EE, Homer R, Flavell RA. IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells. International Immunology 2006, 19: 1-10. PMID: 17101709, DOI: 10.1093/intimm/dxl117.Peer-Reviewed Original ResearchConceptsAirway epithelial cellsLung inflammationTg miceEnhanced lung inflammationEosinophilic lung inflammationEpithelial cellsMast cell hyperplasiaAsthma-like phenotypeRecombinase-activating genes 1IL13 levelsMucus hypersecretionCell hyperplasiaInflammatory cytokinesLung pathologyLung sectionsT cellsMast cellsMucus productionIL13 expressionB cellsLung epitheliumTransgenic miceInflammationIL13LungTransgenic 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
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
Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung
Lee CG, Link H, Baluk P, Homer RJ, Chapoval S, Bhandari V, Kang MJ, Cohn L, Kim YK, McDonald DM, Elias JA. Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nature Medicine 2004, 10: 1095-1103. PMID: 15378055, PMCID: PMC3434232, DOI: 10.1038/nm1105.Peer-Reviewed Original ResearchConceptsTh2 inflammationAntigen sensitizationT helper type 2 cellsAntigen-induced inflammationAsthma-like phenotypeType 2 cellsRole of VEGFMucus metaplasiaDendritic cellsAsthmatic lungCytokine productionTh1 cellsVascular remodelingInflammationTransgenic micePhysiologic dysregulationMyocyte hyperplasiaExaggerated levelsVEGFEpithelial cellsSensitizationAsthmaTh2VEGF regulationLung
2003
Pulmonary Expression of Leukemia Inhibitory Factor Induces B Cell Hyperplasia and Confers Protection in Hyperoxia*
Wang J, Chen Q, Corne J, Zhu Z, Lee CG, Bhandari V, Homer RJ, Elias JA. Pulmonary Expression of Leukemia Inhibitory Factor Induces B Cell Hyperplasia and Confers Protection in Hyperoxia*. Journal Of Biological Chemistry 2003, 278: 31226-31232. PMID: 12782633, DOI: 10.1074/jbc.m301820200.Peer-Reviewed Original ResearchConceptsLeukemia inhibitory factorB-cell hyperplasiaCell hyperplasiaIL-6Protective effectTransgenic miceAlveolar-capillary protein leakB cell-mediated responsesInhibitory factorAdult respiratory distress syndromeHyperoxic acute lung injuryAcute lung injuryRespiratory distress syndromeCell-mediated responsesInduction of interleukinBronchoalveolar lavage cellularityHuman leukemia inhibitory factorLung injuryDistress syndromeLavage cellularityPulmonary expressionProtein leakRespiratory effectsOxidant injuryB lymphocytesTransgenic Modeling of Interleukin-13 in the Lung
Elias JA, Zheng T, Lee CG, Homer RJ, Chen Q, Ma B, Blackburn M, Zhu Z. Transgenic Modeling of Interleukin-13 in the Lung. CHEST Journal 2003, 123: 339s-345s. PMID: 12628968, DOI: 10.1378/chest.123.3_suppl.339s.Peer-Reviewed Original ResearchConceptsChemokine receptor 2Vascular endothelial growth factorIL-13 inducesRegulation of inflammationGrowth factor-β1Endothelial growth factorOverexpression transgenic miceAsthma pathogenesisMurine airwaysKey cytokineInterleukin-13Receptor 2Factor-β1Transgenic miceIL-11Transgenic modelingLungGrowth factorPhenotypic alterationsGenetic targetsAirwayInflammationInterleukinStudy resultsCytokines
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 mechanisms
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-11FibrosisIL-11: Insights in asthma from overexpression transgenic modeling
Zheng T, Zhu Z, Wang J, Homer R, Elias J. IL-11: Insights in asthma from overexpression transgenic modeling. Journal Of Allergy And Clinical Immunology 2001, 108: 489-496. PMID: 11590369, DOI: 10.1067/mai.2001.118510.Peer-Reviewed Original ResearchConceptsIL-11Potential effector functionsMajor basic proteinMurine findingsAirway obstructionSevere asthmaAsthmatic airwaysSubepithelial fibrosisMononuclear infiltrateTissue inflammationFibroblast supernatantsAlveolar developmentVirus infectionPlatelet reconstitutionEffector functionsNonrespiratory tissuesExaggerated quantitiesTransgenic miceDisease severityVariety of stimuliStructural cellsImportant stimulatorSoluble factorsTransgenic modelingEpithelial cellsUse 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
2000
IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury
Corne J, Chupp G, Lee C, Homer R, Zhu Z, Chen Q, Ma B, Du Y, Roux F, McArdle J, Waxman A, Elias J. IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury. Journal Of Clinical Investigation 2000, 106: 783-791. PMID: 10995789, PMCID: PMC381393, DOI: 10.1172/jci9674.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesBlotting, WesternBronchoalveolar Lavage FluidEndothelial Growth FactorsEpithelial CellsFibroblast Growth Factor 10Fibroblast Growth Factor 7Fibroblast Growth FactorsGene Expression RegulationGrowth SubstancesHyperoxiaImmunohistochemistryInterleukin-13LungLymphokinesMacrophagesMiceMice, TransgenicMuscle, SmoothOxygenProtein IsoformsSurvival RateVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsAcute lung injuryHyperoxic acute lung injuryIL-13Lung injuryVEGF accumulationProtective effectTransgenic miceRoom airNontransgenic littermate controlsBreathing room airAcid isoformEndothelial cell growth factorVascular endothelial cell growth factorMice breathing room airCell growth factorBronchoalveolar lavageNontransgenic miceLittermate controlsImportant causeAntibody neutralizationMiceGrowth factorInjuryHyperoxiaSurvivalInterleukin-6–Induced Protection in Hyperoxic Acute Lung Injury
Ward N, Waxman A, Homer R, Mantell L, Einarsson O, Du Y, Elias J. Interleukin-6–Induced Protection in Hyperoxic Acute Lung Injury. American Journal Of Respiratory Cell And Molecular Biology 2000, 22: 535-542. PMID: 10783124, DOI: 10.1165/ajrcmb.22.5.3808.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntioxidantsApoptosisBcl-2-Associated X ProteinBronchoalveolar Lavage FluidCells, CulturedHyperoxiaIn Situ Nick-End LabelingInterleukin-6Lipid PeroxidationLungMiceMice, TransgenicMicroscopy, ElectronProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Superoxide DismutaseTissue Inhibitor of Metalloproteinase-1ConceptsIL-6Lung injuryTransgene (-) animalsAlveolar-capillary protein leakHyperoxic acute lung injurySuperoxide dismutaseAcute lung injuryLung lipid peroxidationHyperoxic lung injurySignificant alterationsBcl-2Cell deathDNA fragmentationProtein leakManganese superoxide dismutaseProtective effectMetalloproteinase-1TIMP-1Transgenic miceTissue inhibitorInjuryZinc superoxide dismutaseMarked diminutionLipid peroxidationCytopathic responseAirway 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