2023
Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination
Suberi A, Grun M, Mao T, Israelow B, Reschke M, Grundler J, Akhtar L, Lee T, Shin K, Piotrowski-Daspit A, Homer R, Iwasaki A, Suh H, Saltzman W. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination. Science Translational Medicine 2023, 15: eabq0603. PMID: 37585505, PMCID: PMC11137749, DOI: 10.1126/scitranslmed.abq0603.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Lethal viral challengeAntigen-presenting cellsSyndrome coronavirus 2Humoral adaptive immunityLung-targeting deliveryIntranasal vaccinationMucosal vaccinationPulmonary diseaseMucosal vaccinesSusceptible miceCoronavirus 2Viral challengeAdaptive immunityLungTranslational potentialMessenger RNA (mRNA) therapeuticsVaccinationMRNADeliveryTherapeuticsRNA therapeuticsTherapeutic delivery
2007
P21 Regulates TGF-β1–Induced Pulmonary Responses via a TNF-α–Signaling Pathway
Yamasaki M, Kang HR, Homer RJ, Chapoval SP, Cho SJ, Lee BJ, Elias JA, Lee CG. P21 Regulates TGF-β1–Induced Pulmonary Responses via a TNF-α–Signaling Pathway. American Journal Of Respiratory Cell And Molecular Biology 2007, 38: 346-353. PMID: 17932374, PMCID: PMC2258454, DOI: 10.1165/rcmb.2007-0276oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCrosses, GeneticCyclin-Dependent Kinase Inhibitor p21DoxycyclineFibrosisImmunohistochemistryInflammationLungMiceMice, Inbred C57BLMice, TransgenicRandom AllocationRNA, MessengerSignal TransductionStatistics as TopicTransforming Growth Factor beta1Tumor Necrosis Factor-alphaConceptsMurine lungCyclin-dependent kinase inhibitorAbsence of p21Caspase-3 activationP21 locusKey regulatorTNF-alpha expressionEffects of TGFExpression of p21Negative modulatorAlveolar destructionLung inflammationTransgenic overexpressionParenchymal destructionPulmonary responseApoptosisRepair responseP21 expressionRegulatory cytokinesMyofibroblast accumulationP21TGF-β1Epithelial cellsEpithelial apoptosisKinase inhibitors
2006
Hyperoxia causes angiopoietin 2–mediated acute lung injury and necrotic cell death
Bhandari V, Choo-Wing R, Lee CG, Zhu Z, Nedrelow JH, Chupp GL, Zhang X, Matthay MA, Ware LB, Homer RJ, Lee PJ, Geick A, de Fougerolles AR, Elias JA. Hyperoxia causes angiopoietin 2–mediated acute lung injury and necrotic cell death. Nature Medicine 2006, 12: 1286-1293. PMID: 17086189, PMCID: PMC2768268, DOI: 10.1038/nm1494.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-2AnimalsCell DeathHyperoxiaMicePulmonary EdemaRNA, MessengerRNA, Small InterferingConceptsAcute lung injuryHyperoxic acute lung injuryLung injuryPulmonary edemaEpithelial necrosisAlveolar edema fluidSiRNA-treated miceCell deathLung epithelial cellsEndothelial cell apoptosisBronchopulmonary dysplasiaVascular leakAngiopoietin-2Edema fluidOxidant injuryAng2 expressionHyperoxiaAng2Vascular regressionBlood vesselsCell apoptosisInjuryNecrotic cell deathEpithelial cellsCell death pathwaysRole 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 smoke
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 lymphocytesCytokine 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
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
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-11Fibrosis
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-1
1997
Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.
Ray P, Tang W, Wang P, Homer R, Kuhn C, Flavell RA, Elias JA. Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes. Journal Of Clinical Investigation 1997, 100: 2501-2511. PMID: 9366564, PMCID: PMC508450, DOI: 10.1172/jci119792.Peer-Reviewed Original Research