2023
IFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury.
Sun Y, Hu B, Stanley G, Harris ZM, Gautam S, Homer R, Koff JL, Rajagopalan G. IFN-γ Is Protective in Cytokine Release Syndrome-associated Extrapulmonary Acute Lung Injury. American Journal Of Respiratory Cell And Molecular Biology 2023, 68: 75-89. PMID: 36125351, PMCID: PMC9817908, DOI: 10.1165/rcmb.2022-0117oc.Peer-Reviewed Original ResearchConceptsCytokine release syndromeAcute lung injuryExtrapulmonary acute lung injuryIFN-γ KO miceIL-17ALung injuryKO miceStaphylococcal enterotoxin BRelease syndromeIL-17A KO miceSevere acute lung injuryAcute respiratory distress syndromeSystemic T cell activationEnterotoxin BAdaptive T lymphocytesDR3 transgenic miceNeutralization of IFNRespiratory distress syndromeHuman leukocyte antigenRole of IFNT cell cytokinesJanus kinase inhibitorS100A8/A9T cell activationALI parameters
2022
Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis
Damsky W, Wang A, Kim DJ, Young BD, Singh K, Murphy MJ, Daccache J, Clark A, Ayasun R, Ryu C, McGeary MK, Odell ID, Fazzone-Chettiar R, Pucar D, Homer R, Gulati M, Miller EJ, Bosenberg M, Flavell RA, King B. Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. Nature Communications 2022, 13: 3140. PMID: 35668129, PMCID: PMC9170782, DOI: 10.1038/s41467-022-30615-x.Peer-Reviewed Original ResearchConceptsType 1 immunityInternal organ involvementOrgan involvementT cell-derived IFNIdiopathic inflammatory disorderOpen-label trialMonths of treatmentType 1 cytokinesJanus kinase inhibitorImmunologic changesLongstanding sarcoidosisSarcoidosis activitySarcoidosis symptomsClinical improvementCutaneous sarcoidosisSecondary outcomesComplete responsePrimary outcomeTofacitinib treatmentActivity scoreCytokine mediatorsIL-12IL-15IL-6Inflammatory disorders
2012
Susceptibility to Progressive Cryptococcus neoformans Pulmonary Infection Is Regulated by Loci on Mouse Chromosomes 1 and 9
Carroll SF, Lafferty EI, Flaczyk A, Fujiwara TM, Homer R, Morgan K, Loredo-Osti JC, Qureshi ST. Susceptibility to Progressive Cryptococcus neoformans Pulmonary Infection Is Regulated by Loci on Mouse Chromosomes 1 and 9. Infection And Immunity 2012, 80: 4167-4176. PMID: 22988020, PMCID: PMC3497416, DOI: 10.1128/iai.00417-12.Peer-Reviewed Original ResearchConceptsC3H/HeN miceCBA/J miceHeN micePulmonary infectionJ miceFungal burdenSusceptible C3H/HeN miceInterleukin-5Cryptococcus neoformans Pulmonary InfectionIL-13 protein expressionHigher pulmonary expressionLung fungal burdenGoblet cell metaplasiaTh2 immune responsePathogenesis of pneumoniaIL-17 proteinCBA/JCryptococcal pneumoniaGreater airwayTissue neutrophiliaCryptococcal infectionCell metaplasiaIntratracheal infectionPulmonary inflammationTissue eosinophilia
2011
Modern concepts on the role of inflammation in pulmonary fibrosis.
Homer RJ, Elias JA, Lee CG, Herzog E. Modern concepts on the role of inflammation in pulmonary fibrosis. Archives Of Pathology & Laboratory Medicine 2011, 135: 780-8. PMID: 21631273, DOI: 10.5858/2010-0296-ra.1.BooksConceptsRole of inflammationIdiopathic pulmonary fibrosisPulmonary fibrosisTherapeutic interventionsResult of inflammationCell deathLung transplantationCytokine environmentMacrophage polarizationInflammationFibrosisLethal diseaseLimited biomarkersClinical contextDisease biomarkersBiomarkersDeathInterventionUnpublished researchTransplantationLungDisease
2008
A Critical Role of SHP-1 in Regulation of Type 2 Inflammation in the Lung
Oh SY, Zheng T, Kim YK, Cohn L, Homer RJ, McKenzie AN, Zhu Z. A Critical Role of SHP-1 in Regulation of Type 2 Inflammation in the Lung. American Journal Of Respiratory Cell And Molecular Biology 2008, 40: 568-574. PMID: 18952567, PMCID: PMC2677436, DOI: 10.1165/rcmb.2008-0225oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchial HyperreactivityBronchoalveolar Lavage FluidCytokinesEpitheliumHypertrophyLungLymphocyte ActivationMetaplasiaMiceMice, Inbred C57BLMucin 5ACMucusPneumoniaProtein Tyrosine Phosphatase, Non-Receptor Type 6Pulmonary FibrosisSignal TransductionSTAT6 Transcription FactorTh2 CellsConceptsSHP-1Src homology 2 domain-containing protein tyrosine phosphataseProtein tyrosine phosphataseGene deletion approachIL-4/ILViable motheaten miceMev miceCritical roleTyrosine phosphataseKey genesNegative regulatorSignal transducerMolecular mechanismsCytokine receptorsMotheaten miceTranscription 6Critical moleculesDirect roleType 2 inflammationChronic inflammatory disordersHallmark of asthmaLung homeostasisPathwayGrowth factorAirway hyperresponsivenessEnhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection
Guillot L, Carroll SF, Homer R, Qureshi ST. Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection. Infection And Immunity 2008, 76: 4745-4756. PMID: 18678664, PMCID: PMC2546841, DOI: 10.1128/iai.00341-08.Peer-Reviewed Original ResearchConceptsSJL/J miceKC/CXCL1Cryptococcus neoformans infectionC. neoformans infectionKeratinocyte-derived chemokineNeoformans infectionJ miceInnate immune responseTNF-alphaProgressive infectionImmune responseResistant SJL/J miceMIP-2/CXCL2Pulmonary C. neoformans infectionPulmonary Cryptococcus neoformans infectionPulmonary innate immune responseSJL/J macrophagesC. neoformansInflammatory cytokine tumor necrosis factor alphaEnhanced innate immune responseMIP-1alpha/CCL3IL-12/ILMCP-1/CCL2Cytokine tumor necrosis factor alphaTumor necrosis factor alpha
2005
Regulation of lung injury and repair by Toll-like receptors and hyaluronan
Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, Prestwich GD, Mascarenhas MM, Garg HG, Quinn DA, Homer RJ, Goldstein DR, Bucala R, Lee PJ, Medzhitov R, Noble PW. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nature Medicine 2005, 11: 1173-1179. PMID: 16244651, DOI: 10.1038/nm1315.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryToll-like receptorsInflammatory responseTLR2-dependent mannerSera of individualsCell-specific overexpressionEpithelial cell apoptosisEpithelial cell integrityHyaluronan degradation productsChemokine productionInflammatory cellsTissue injuryExtracellular matrix glycosaminoglycan hyaluronanTransepithelial migrationInjuryCell surface hyaluronanHyaluronan fragmentsCell apoptosisBasal activationClearance resultsInflammationGlycosaminoglycan hyaluronanReceptorsHyaluronan
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
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
Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13–induced inflammation and remodeling
Lanone S, Zheng T, Zhu Z, Liu W, Lee CG, Ma B, Chen Q, Homer RJ, Wang J, Rabach LA, Rabach ME, Shipley JM, Shapiro SD, Senior RM, Elias JA. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13–induced inflammation and remodeling. Journal Of Clinical Investigation 2002, 110: 463-474. PMID: 12189240, PMCID: PMC150413, DOI: 10.1172/jci14136.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementChemotaxis, LeukocyteCytokinesEndopeptidasesFibrosisInflammationInterleukin-13LungLung ComplianceLung DiseasesMatrix Metalloproteinase 12Matrix Metalloproteinase 9MetalloendopeptidasesMiceMice, KnockoutMice, TransgenicPulmonary AlveoliRespiratory InsufficiencyRespiratory MucosaConceptsIL-13-induced inflammationMMP-9IL-13MMP-12MMP-2Respiratory failureAlveolar remodelingMatrix metalloproteinasesIL-13 transgenic miceMMP-12-deficient miceAccumulation of eosinophilsBronchoalveolar lavage fluidIL-13 actsIL-13 inductionMatrix metalloproteinases-9Recovery of leukocytesLung enlargementLymphocytic inflammationNeutrophil accumulationLymphocyte recoveryLavage fluidTotal leukocytesInflammatory effectsAlveolar enlargementMetalloproteinases-9
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 inflammationCONSEQUENCES OF LONG-TERM INFLAMMATION Airway Remodeling
Homer R, Elias J. CONSEQUENCES OF LONG-TERM INFLAMMATION Airway Remodeling. Clinics In Chest Medicine 2000, 21: 331-343. PMID: 10907592, DOI: 10.1016/s0272-5231(05)70270-7.Peer-Reviewed Original ResearchConceptsAirway remodelingAirway chronic inflammationEffect of therapyAirway inflammationAsthmatic patientsAppropriate therapyChronic inflammationClinical manifestationsSmooth muscleCollagen depositionExperimental modelMucus glandsBiologic dataRemodelingAirwayInflammationTherapyAsthmaticsAsthmaPatientsNoncollagenous matrix
1999
Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production
Zhu Z, Homer R, Wang Z, Chen Q, Geba G, Wang J, Zhang Y, Elias J. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. Journal Of Clinical Investigation 1999, 103: 779-788. PMID: 10079098, PMCID: PMC408149, DOI: 10.1172/jci5909.Peer-Reviewed Original ResearchConceptsMucus cell metaplasiaAirway hyperresponsivenessIL-13Airway fibrosisCell metaplasiaPulmonary expressionCharcot-LeydenInflammatory responseBaseline airway resistanceSubepithelial airway fibrosisTransgene-negative littermatesVivo effector functionNonspecific airway hyperresponsivenessTransgene-positive miceEosinophilic inflammatory responseEpithelial cell hypertrophyGranulocyte-macrophage colony-stimulating factorTransgene-positive animalsColony-stimulating factorClara cell 10Cause inflammationMucus hypersecretionSubepithelial fibrosisAirway resistanceEotaxin production
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