2019
Transcriptional regulatory model of fibrosis progression in the human lung
McDonough JE, Ahangari F, Li Q, Jain S, Verleden SE, Herazo-Maya J, Vukmirovic M, DeIuliis G, Tzouvelekis A, Tanabe N, Chu F, Yan X, Verschakelen J, Homer RJ, Manatakis DV, Zhang J, Ding J, Maes K, De Sadeleer L, Vos R, Neyrinck A, Benos PV, Bar-Joseph Z, Tantin D, Hogg JC, Vanaudenaerde BM, Wuyts WA, Kaminski N. Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight 2019, 4 PMID: 31600171, PMCID: PMC6948862, DOI: 10.1172/jci.insight.131597.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced fibrosisAlveolar surface densityFibrosis progressionLung fibrosisHuman lungDynamic Regulatory Events MinerExtent of fibrosisIPF lungsPulmonary fibrosisControl lungsIPF tissueB lymphocytesFibrosisLungLinear mixed-effects modelsMixed-effects modelsGene expression changesSystems biology modelsDifferential gene expression analysisGene expression analysisProgressionGene expression networksRNA sequencingBiology models
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 ResearchMeSH KeywordsAnimalsAsthmaGene Expression RegulationGlycoproteinsHumansMiceMice, Inbred C57BLMice, KnockoutMyelin ProteinsNogo ProteinsPhosphoproteinsTh2 CellsConceptsLung inflammationTh2-mediated lung inflammationSevere human asthmaAsthma-like phenotypeNonallergic miceHuman asthmaInflammation resultsKO miceLung tissueNogo expressionAirway epitheliumSmooth muscleReticulon 4BTransgenic miceLung epitheliumEpithelial reconstitutionMiceMarked reductionProtective genesEndogenous regulatorNogoInflammationLungPLUNCTransgenic expression
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 lung
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
2005
Inhibition of the Src and Jak Kinases Protects against Lipopolysaccharide-induced Acute Lung Injury
Severgnini M, Takahashi S, Tu P, Perides G, Homer RJ, Jhung JW, Bhavsar D, Cochran BH, Simon AR. Inhibition of the Src and Jak Kinases Protects against Lipopolysaccharide-induced Acute Lung Injury. American Journal Of Respiratory And Critical Care Medicine 2005, 171: 858-867. PMID: 15665321, DOI: 10.1164/rccm.200407-981oc.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsCapillary Leak SyndromeEnzyme ActivationEnzyme InhibitorsEscherichia coliGene Expression RegulationGene Transfer TechniquesIndolesJanus Kinase 2LipopolysaccharidesLungMiceMice, Inbred BALB CProtein-Tyrosine KinasesProto-Oncogene ProteinsRespiratory Distress SyndromeSignal TransductionSrc-Family KinasesSulfonamidesTranscriptional ActivationTyrphostinsConceptsAcute lung injuryLung injuryCytokine productionLPS challengeSmall molecule inhibitorsLipopolysaccharide-induced acute lung injuryLethal LPS challengeLung cytokine productionSystemic cytokine productionSelective tyrosine kinase inhibitorLung vascular permeabilityMurine lung injuryTyrosine kinase inhibitorsNovel therapeutic agentsMolecule inhibitorsSuppressor of cytokineChemokine productionSystemic inhibitionAirway epitheliumVascular permeabilitySpecific small molecule inhibitorsInjurySrc kinaseTherapeutic agentsKinase inhibitors
2003
Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro
Zheng T, Zhu Z, Liu W, Lee CG, Chen Q, Homer RJ, Elias JA. Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro. Journal Of Allergy And Clinical Immunology 2003, 111: 720-728. PMID: 12704349, DOI: 10.1067/mai.2003.1383.Peer-Reviewed Original ResearchConceptsIL-13Ralpha1 mRNAIL-13IL-13Ralpha2IL-13Ralpha1IL-4IFN-gammaRegulatory eventsTransgenic IL-13Epithelial cellsIL-13 responsesMRNA accumulationAirway epithelial cellsSites of inflammationIL-13 signalsIL-13 stimulationHigh-affinity receptorIL-10Lung fragmentsControl miceOverexpression miceIL-13Rα2Cytokine regulationIL-4RalphaIL-13Rα1Receptor subunits
2002
Cytokine Regulation of Mucus Production in a Model of Allergic Asthma
Cohn L, Whittaker L, Niu N, Homer RJ. Cytokine Regulation of Mucus Production in a Model of Allergic Asthma. Novartis Foundation Symposia 2002, 248: 201-220. PMID: 12568496, DOI: 10.1002/0470860790.ch13.BooksMeSH KeywordsAdministration, InhalationAnimalsAsthmaBronchoalveolar Lavage FluidCells, CulturedExocytosisGene Expression RegulationImmunizationInterferon-gammaInterferonsInterleukin-13Interleukin-13 Receptor alpha1 SubunitInterleukin-4Interleukin-5Interleukin-9Mast CellsMiceMice, TransgenicModels, AnimalMucinsMucusOvalbuminPeptide FragmentsPulmonary EosinophiliaRadiation ChimeraReceptors, Antigen, T-Cell, alpha-betaReceptors, InterleukinReceptors, Interleukin-13Receptors, Interleukin-4Respiratory SystemSignal TransductionTh1 CellsTh2 CellsConceptsAirway inflammationTh2 cellsMucus productionTh1 cellsT cell receptor transgenic CD4Airway inflammatory infiltrateDifferent lymphocyte subsetsBone marrow chimerasAbsence of interleukinAirway obstructionAllergic asthmaLymphocyte subsetsEosinophilic inflammationMucus hyperproductionInflammatory infiltrateClinical symptomsInflammatory cellsTh2 lymphocytesRecipient miceTh cellsTransgenic CD4Respiratory tractMast cellsCytokine regulationInflammationInterleukin-13 Mediates a Fundamental Pathway for Airway Epithelial Mucus Induced by CD4 T Cells and Interleukin-9
Whittaker L, Niu N, Temann U, Stoddard A, Flavell RA, Ray A, Homer RJ, Cohn L. Interleukin-13 Mediates a Fundamental Pathway for Airway Epithelial Mucus Induced by CD4 T Cells and Interleukin-9. American Journal Of Respiratory Cell And Molecular Biology 2002, 27: 593-602. PMID: 12397019, DOI: 10.1165/rcmb.4838.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCells, CulturedGene Expression RegulationInterferon-gammaInterleukin-13Interleukin-9LungMiceMice, Inbred BALB CMice, Mutant StrainsMice, TransgenicMucin 5ACMucinsNF-kappa BReceptors, InterferonReceptors, Interleukin-4Recombinant ProteinsRespiratory MucosaSignal TransductionTh2 CellsConceptsIL-13Th2 cellsTh2-induced airway inflammationEpithelial mucusCD4 Th cellsCD4 T cellsAbsence of interleukinIL-13 actsNuclear factor-kappaBAsthma resultsTh2 effectsAirway inflammationMucus hyperproductionNegative infectionsTh cytokinesInflammatory cellsRecipient miceTh cellsIL-4IL-5Respiratory tractAirway epitheliumIL-9T cellsComplete blockadeTransgenic 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
Use 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
Endogenous and Exogenous IL-6 Inhibit Aeroallergen-Induced Th2 Inflammation
Wang J, Homer R, Chen Q, Elias J. Endogenous and Exogenous IL-6 Inhibit Aeroallergen-Induced Th2 Inflammation. The Journal Of Immunology 2000, 165: 4051-4061. PMID: 11034416, DOI: 10.4049/jimmunol.165.7.4051.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAerosolsAllergensAnimalsBronchial HyperreactivityChemokinesCytokinesGene Expression RegulationInflammationInterleukin-6LungMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAMice, KnockoutMice, TransgenicOvalbuminPlethysmography, Whole BodyPulmonary EosinophiliaRNA, MessengerTh2 CellsVascular Cell Adhesion Molecule-1ConceptsIL-6Wild-type miceIL-13 proteinTh2 inflammationBronchoalveolar lavageIL-4IL-5IFN-gammaSensitized wild-type miceIL-6-deficient miceMonocyte chemoattractant protein-1Exaggerated airway responseTh2-dominated inflammationBALB/c backgroundInflammatory protein-1alphaChemoattractant protein-1IL-6 productionExogenous IL-6Endothelial VCAM-1Airway responsesAirway responsivenessAsthmatic airwaysExaggerated inflammationDeficient miceVCAM-1IL-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 factorInjuryHyperoxiaSurvivalIL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production
Wang J, Homer R, Hong L, Cohn L, Lee C, Jung S, Elias J. IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production. The Journal Of Immunology 2000, 165: 2222-2231. PMID: 10925310, DOI: 10.4049/jimmunol.165.4.2222.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAerosolsAllergensAnimalsBronchoalveolar Lavage FluidCytokinesGene Expression RegulationHumansImmunizationInterleukin-11MiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAMice, TransgenicMucinsMucusOvalbuminPulmonary EosinophiliaRecombinant ProteinsRespiratory MucosaSpecies SpecificityTh2 CellsTurkeysVascular Cell Adhesion Molecule-1ConceptsTh2 cell accumulationIL-11OVA challengeMucus hypersecretionIL-4IL-5VCAM-1Cell accumulationMucin 5AC (MUC5AC) gene expressionVCAM-1 gene expressionAg-specific IgEBronchoalveolar lavage (BAL) inflammationLung IL-4Th2 cytokine productionIFN-gamma productionEndothelial-cell VCAM-1IL-13 mRNAIL-13 proteinChemoattractant protein 2Chemoattractant protein-3Mucus metaplasiaTh1 inflammationPulmonary eosinophiliaTh2 inflammationAirway inflammation
1999
Inhibition of Allergic Inflammation in a Murine Model of Asthma by Expression of a Dominant-Negative Mutant of GATA-3
Zhang D, Yang L, Cohn L, Parkyn L, Homer R, Ray P, Ray A. Inhibition of Allergic Inflammation in a Murine Model of Asthma by Expression of a Dominant-Negative Mutant of GATA-3. Immunity 1999, 11: 473-482. PMID: 10549629, DOI: 10.1016/s1074-7613(00)80122-3.Peer-Reviewed Original ResearchMeSH KeywordsAerosolsAmino Acid SubstitutionAnimalsAsthmaBronchoalveolar Lavage FluidDNA-Binding ProteinsDrug HypersensitivityEosinophiliaGATA3 Transcription FactorGene Expression RegulationGenes, DominantImmunizationImmunoglobulin EInflammationInterleukin-13Interleukin-4Interleukin-5LungMiceMice, Inbred C57BLMice, TransgenicMucusMutagenesis, Site-DirectedOvalbuminTh2 CellsTrans-ActivatorsConceptsCytokines IL-4GATA-3IL-13IL-4IL-5Th2 cytokines IL-4Pathogenesis of asthmaTreatment of asthmaTranscription factor GATA-3Potential therapeutic targetAirway eosinophiliaTh2 responsesAllergic inflammationAllergic diseasesTh2 cytokinesT-cell-specific fashionTh1 cellsIgE synthesisTh2 cellsMucus productionMurine modelTherapeutic targetTransgenic miceAsthmaDominant negative mutant
1996
Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.
Tang W, Geba GP, Zheng T, Ray P, Homer RJ, Kuhn C, Flavell RA, Elias JA. Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction. Journal Of Clinical Investigation 1996, 98: 2845-2853. PMID: 8981933, PMCID: PMC507752, DOI: 10.1172/jci119113.Peer-Reviewed Original ResearchMeSH KeywordsAirway ObstructionAirway ResistanceAnimalsBlotting, NorthernBlotting, SouthernCloning, MolecularDisease Models, AnimalGene Expression RegulationHistocytochemistryImmunohistochemistryInterleukin-11LungMethacholine ChlorideMiceMice, TransgenicMicroscopy, ElectronPromoter Regions, GeneticProteinsPulmonary FibrosisUteroglobinConceptsIL-11Fibrotic responseTransgene miceAlpha-smooth muscle actinMononuclear cell infiltratePotential effector functionsSmooth muscle actinTargeted expressionSmooth muscle cellsHuman airway disordersType IIILung stromal cellsAirway disordersLymphocytic inflammationCell infiltrateSubepithelial fibrosisAirway resistanceRespiratory virusesMouse airwaysMurine airwaysInflammatory fociPhysiologic evaluationInflammatory responseBronchial remodelingMHC class
1985
Genetic, Serological and Functional Analysis of I‐J Molecules
Murphy D, Horowitz M, Homer R, Flood P. Genetic, Serological and Functional Analysis of I‐J Molecules. Immunological Reviews 1985, 83: 79-103. PMID: 3160653, DOI: 10.1111/j.1600-065x.1985.tb00471.x.Peer-Reviewed Original Research