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
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 lungIL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung
Zheng T, Liu W, Oh SY, Zhu Z, Hu B, Homer RJ, Cohn L, Grusby MJ, Elias JA. IL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung. The Journal Of Immunology 2008, 180: 522-529. PMID: 18097054, DOI: 10.4049/jimmunol.180.1.522.Peer-Reviewed Original ResearchConceptsIL-13Ralpha2Pulmonary inflammationIL-13Inflammatory responseMurine lungHigh-affinity IL-13 receptorsTransgenic IL-13IL-13 receptor α2Production of chemokinesEnhanced inflammatory responseIL-13 receptorMucus metaplasiaTh2 inflammationAirway remodelingSubepithelial fibrosisIL-4Receptor α2Critical cytokineIL-13Ralpha1IL-4RalphaDecoy receptorPhysiologic responsesInflammationTissue effectsReceptors
2006
Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation
Homer RJ, Zhu Z, Cohn L, Lee CG, White WI, Chen S, Elias JA. Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2006, 291: l502-l511. PMID: 16556727, DOI: 10.1152/ajplung.00364.2005.Peer-Reviewed Original ResearchConceptsAirway epithelial cellsAllergic inflammationEpithelial cellsT-helper 2 inflammationClara cell secretory proteinProximal airway epithelial cellsDistal airway epitheliumMammalian chitinase familyMurine airway epithelial cellsIL-13 signalingProduction of mucusExpression of FOXA2Th1 inflammationTh2 inflammationDistal cellsAcidic mammalian chitinaseDistal airwaysPositive molecular markersAirway epitheliumInflammationAlveolar macrophagesProtein-expressing cellsMicrofilarial sheathMammalian chitinaseAMCase
2004
Acidic Mammalian Chitinase in Asthmatic Th2 Inflammation and IL-13 Pathway Activation
Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L, Hamid Q, Elias JA. Acidic Mammalian Chitinase in Asthmatic Th2 Inflammation and IL-13 Pathway Activation. Science 2004, 304: 1678-1682. PMID: 15192232, DOI: 10.1126/science.1095336.Peer-Reviewed Original ResearchConceptsTh2 inflammationAcidic mammalian chitinaseIL-13-induced responsesPathway activationTh2-dominated disordersMammalian chitinaseAirway hyperresponsivenessAsthma modelT helperHuman asthmaChemokine inductionInterleukin-13Exaggerated quantitiesImportant mediatorEpithelial cellsAsthmaInflammationActivationHyperresponsivenessInfection
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 regulationInflammation
2001
IL-4 Promotes Airway Eosinophilia by Suppressing IFN-γ Production: Defining a Novel Role for IFN-γ in the Regulation of Allergic Airway Inflammation
Cohn L, Herrick C, Niu N, Homer R, Bottomly K. IL-4 Promotes Airway Eosinophilia by Suppressing IFN-γ Production: Defining a Novel Role for IFN-γ in the Regulation of Allergic Airway Inflammation. The Journal Of Immunology 2001, 166: 2760-2767. PMID: 11160342, DOI: 10.4049/jimmunol.166.4.2760.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, CutaneousAdministration, IntranasalAdoptive TransferAnimalsBone Marrow CellsBone Marrow TransplantationBronchiCell MovementDown-RegulationEosinophilsFemaleHematopoietic Stem CellsInflammationInterferon-gammaInterleukin-13Interleukin-4Interleukin-5MaleMiceMice, Inbred BALB CMice, KnockoutMice, TransgenicOvalbuminPulmonary EosinophiliaReceptors, InterferonRespiratory HypersensitivityTh2 CellsUp-RegulationConceptsAirway eosinophiliaIL-4IFN-gammaTh2 cellsAirway eosinophilsIL-5Allergic airway inflammationIFN-γ productionTh2 cell generationAirway inflammationEosinophilic inflammationLung eosinophiliaLung parenchymalTh2 cytokinesIntranasal administrationRespiratory tractLung tissueCounterregulatory effectsEosinophiliaCell transferEosinophilsHemopoietic cellsInflammationAirwayIFN
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-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
T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production
Cohn L, Homer R, Niu N, Bottomly K. T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production. Journal Of Experimental Medicine 1999, 190: 1309-1318. PMID: 10544202, PMCID: PMC2195688, DOI: 10.1084/jem.190.9.1309.Peer-Reviewed Original ResearchConceptsTh1 cellsTh2 cellsMucus productionAirway eosinophiliaIFN-gammaRecipient miceAirway inflammationIFN-gamma receptor signalingT helper type 1T helper 1 cellsAllergic airway inflammationTh2 cytokine secretionHelper type 1Different inhibitory pathwaysAsthmatic patientsPathologic featuresCytokine secretionInflammatory responseRespiratory tractEosinophiliaInhibitory pathwaysMouse modelInflammationType 1Marked reductionInhibition 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 mutantTh2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils.
Cohn L, Homer RJ, MacLeod H, Mohrs M, Brombacher F, Bottomly K. Th2-induced airway mucus production is dependent on IL-4Ralpha, but not on eosinophils. The Journal Of Immunology 1999, 162: 6178-83. PMID: 10229862, DOI: 10.4049/jimmunol.162.10.6178.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAnimalsAsthmaBronchiEosinophiliaEosinophilsInterleukin-13 Receptor alpha1 SubunitInterleukin-4Interleukin-5Mast CellsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Mutant StrainsMice, TransgenicMucusOvalbuminReceptors, InterleukinReceptors, Interleukin-13Receptors, Interleukin-4Th2 CellsConceptsMucus productionTh2 cellsAirway eosinophiliaAirway inflammationIL-4RalphaAirway mucus productionCD4 Th2 cellsAirway obstructionBAL eosinophiliaHuman asthmaticsMucus hyperproductionClinical symptomsIL-13Recipient miceTh1 cellsIL-4IL-5Respiratory tractEosinophiliaMast cellsAnimal modelsEosinophilsMarked increaseCell stimulationMucus
1998
Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation
Yang L, Cohn L, Zhang D, Homer R, Ray A, Ray P. Essential Role of Nuclear Factor κB in the Induction of Eosinophilia in Allergic Airway Inflammation. Journal Of Experimental Medicine 1998, 188: 1739-1750. PMID: 9802985, PMCID: PMC2212522, DOI: 10.1084/jem.188.9.1739.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAsthmaBase SequenceChemokine CCL11Chemokines, CCCytokinesDNA PrimersEosinophiliaGene ExpressionInflammationIntercellular Adhesion Molecule-1Interleukin-4Interleukin-5LungMiceMice, Inbred C57BLMice, KnockoutNF-kappa BNF-kappa B p50 SubunitOvalbuminReverse Transcriptase Polymerase Chain ReactionTh2 CellsVascular Cell Adhesion Molecule-1ConceptsAirway inflammationEosinophil-rich airway inflammationTh2 cytokine interleukin-5Adhesion molecules VCAM-1Chemokine macrophage inflammatory proteinCell adhesion molecule VCAM-1Allergic airway inflammationEosinophilic airway inflammationT cell primingPathogenesis of asthmaT helper 2T cell recruitmentInduction of eosinophiliaMacrophage inflammatory proteinCytokines interleukin-5Wild-type miceSites of inflammationNuclear factor κBAllergic asthmaAsthmatic airwaysHelper 2Cell primingInflammatory proteinMIP-1betaExtravasation of eosinophils
1997
Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production
Cohn L, Homer R, Marinov A, Rankin J, Bottomly K. Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production. Journal Of Experimental Medicine 1997, 186: 1737-1747. PMID: 9362533, PMCID: PMC2199146, DOI: 10.1084/jem.186.10.1737.Peer-Reviewed Original ResearchConceptsTh2 cellsMucus productionAirway inflammationIL-4Asthmatic patientsCell recruitmentOVA-specific Th2 cellsT helper 2 cellsIL-4-deficient miceAirway mucus productionOVA-specific TCRRole of Th1CD4 T cellsImportant clinical symptomInduction of inflammationTh2 cell recruitmentCD4 Th1Airway biopsiesClinical symptomsTh1 cellsTNF-alphaT cellsInterleukin-4Effector functionsMucus secretion