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
Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report
Kulkarni HS, Lee JS, Bastarache JA, Kuebler WM, Downey GP, Albaiceta GM, Altemeier WA, Artigas A, Bates JHT, Calfee CS, Dela Cruz CS, Dickson RP, Englert JA, Everitt JI, Fessler MB, Gelman AE, Gowdy KM, Groshong SD, Herold S, Homer RJ, Horowitz JC, Hsia CCW, Kurahashi K, Laubach VE, Looney MR, Lucas R, Mangalmurti NS, Manicone AM, Martin TR, Matalon S, Matthay MA, McAuley DF, McGrath-Morrow SA, Mizgerd JP, Montgomery SA, Moore BB, Noël A, Perlman CE, Reilly JP, Schmidt EP, Skerrett SJ, Suber TL, Summers C, Suratt BT, Takata M, Tuder R, Uhlig S, Witzenrath M, Zemans RL, Matute-Bello G. Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report. American Journal Of Respiratory Cell And Molecular Biology 2022, 66: e1-e14. PMID: 35103557, PMCID: PMC8845128, DOI: 10.1165/rcmb.2021-0531st.Peer-Reviewed Original ResearchConceptsExperimental acute lung injuryAcute lung injuryAcute respiratory distress syndromeRespiratory distress syndromeLung injuryDistress syndromeOfficial American Thoracic Society Workshop ReportHuman acute respiratory distress syndromeAlveolar-capillary barrierKey pathophysiologic featuresAspects of injury
2016
Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice
Sureshbabu A, Syed M, Das P, Janér C, Pryhuber G, Rahman A, Andersson S, Homer RJ, Bhandari V. Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice. American Journal Of Respiratory Cell And Molecular Biology 2016, 55: 722-735. PMID: 27374190, PMCID: PMC5105179, DOI: 10.1165/rcmb.2015-0349oc.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAdaptor Proteins, Signal TransducingAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisAutophagyBronchopulmonary DysplasiaCell LineFemaleHumansHyperoxiaHypertension, PulmonaryHypertrophy, Right VentricularInfant, NewbornLungMiceMicrotubule-Associated ProteinsNaphthyridinesPhenotypeRegulatory-Associated Protein of mTORTime FactorsTumor Suppressor Protein p53ConceptsAcute lung injuryBronchopulmonary dysplasiaLung injuryWild-type miceMechanistic targetRegulatory-Associated ProteinLysosomal-associated membrane protein 1Apoptotic cell deathFetal type II alveolar epithelial cellsMouse lungRole of autophagyHyperoxia-Induced Lung InjuryLight chain 3Activation of autophagyType II alveolar epithelial cellsRespiratory distress syndromeMembrane protein 1Developmental lung diseaseUseful therapeutic targetNeonatal mouse lungAlveolar epithelial cellsPharmacological inhibitorsTreatment of hyperoxiaCell deathAutophagic flux
2015
Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung
Sureshbabu A, Syed MA, Boddupalli CS, Dhodapkar MV, Homer RJ, Minoo P, Bhandari V. Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung. Respiratory Research 2015, 16: 4. PMID: 25591994, PMCID: PMC4307226, DOI: 10.1186/s12931-014-0162-6.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisDisease Models, AnimalGenotypeHumansHyperoxiaLungMice, Inbred C57BLMice, KnockoutMice, TransgenicPhenotypePneumoniaProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionTime FactorsTransforming Growth Factor beta1Up-RegulationConceptsImpaired alveolarizationBronchopulmonary dysplasiaAlveolar epithelial cellsPulmonary inflammationPulmonary phenotypeMouse lungAcute lung injuryType II alveolar epithelial cellsApoptotic cell deathCell deathNewborn mouse lungPotential therapeutic strategyGrowth factor betaNull mutant miceLung injuryImproved survivalNeonatal mortalityMonocyte infiltrationAbnormal alveolarizationAngiogenic mediatorsInflammatory signalsTGFβ1 expressionTherapeutic strategiesInflammatory macrophagesLung morphometry
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
2012
Increased Hyperoxia-Induced Lung Injury in Nitric Oxide Synthase 2 Null Mice Is Mediated via Angiopoietin 2
Bhandari V, Choo-Wing R, Harijith A, Sun H, Syed MA, Homer RJ, Elias JA. Increased Hyperoxia-Induced Lung Injury in Nitric Oxide Synthase 2 Null Mice Is Mediated via Angiopoietin 2. American Journal Of Respiratory Cell And Molecular Biology 2012, 46: 668-676. PMID: 22227562, PMCID: PMC3359903, DOI: 10.1165/rcmb.2011-0074oc.Peer-Reviewed Original ResearchConceptsHyperoxic acute lung injuryNOS/nitric oxideNitric oxideLung injuryAngiopoietin-2Pathogenesis of HALIAlveolar-capillary protein leakAcute respiratory distress syndromeHyperoxia-Induced Lung InjuryAcute lung injuryRespiratory distress syndromeImportant protective roleCell deathBronchopulmonary dysplasiaDistress syndromeSupplemental oxygenNb miceProtein leakTissue injuryProtective roleNewbornsNull micePremature deathAdult controlsAng2
2010
Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4
Jiang D, Liang J, Campanella GS, Guo R, Yu S, Xie T, Liu N, Jung Y, Homer R, Meltzer EB, Li Y, Tager AM, Goetinck PF, Luster AD, Noble PW. Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4. Journal Of Clinical Investigation 2010, 120: 2049-2057. PMID: 20484822, PMCID: PMC2877927, DOI: 10.1172/jci38644.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisCXCL10 proteinAcute lung injuryExcess extracellular matrix productionLung fibroblast migrationSyndecan-4Myofibroblast recruitmentLung injuryLung functionSubsequent fibrosisNeutrophil recruitmentInterstitial fibrosisWT miceIntratracheal instillationSyndecan-4 expressionNovel therapiesMigration of fibroblastsFibrosisBleomycin treatmentCXCL10Fibroblast recruitmentExtracellular matrix productionHeparan sulfate proteoglycan syndecan-4Interstitial compartmentMice
2007
Increased Hyperoxia-Induced Mortality and Acute Lung Injury in IL-13 Null Mice
Bhandari V, Choo-Wing R, Homer RJ, Elias JA. Increased Hyperoxia-Induced Mortality and Acute Lung Injury in IL-13 Null Mice. The Journal Of Immunology 2007, 178: 4993-5000. PMID: 17404281, DOI: 10.4049/jimmunol.178.8.4993.Peer-Reviewed Original ResearchConceptsEndogenous IL-13Acute lung injuryIL-13Lung injuryIL-13RNull miceHyperoxic acute lung injuryInhibition of injuryBronchoalveolar lavage fluidInduction of inflammationEndothelial cell growth factorVascular endothelial cell growth factorIL-13 locusCell growth factorTh2 inflammationLavage fluidIL-6Tissue inflammationVariety of diseasesIL-13Ralpha1Diseased lungsIL-4RalphaInflammationInjuryIL-11
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 ResearchConceptsAcute 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 pathways
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 hyaluronanReceptorsHyaluronanBcl-2–related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury
He CH, Waxman AB, Lee CG, Link H, Rabach ME, Ma B, Chen Q, Zhu Z, Zhong M, Nakayama K, Nakayama KI, Homer R, Elias JA. Bcl-2–related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury. Journal Of Clinical Investigation 2005, 115: 1039-1048. PMID: 15841185, PMCID: PMC1070412, DOI: 10.1172/jci23004.Peer-Reviewed Original ResearchConceptsHyperoxic acute lung injuryAcute lung injuryLung injuryIL-11Bcl-2Alveolar protein leakBcl-xLToxic effectsEpithelial cell apoptosisWT miceProtein leakMurine survivalExpression of A1Survival advantageBfl-1/A1Protective responsePremature deathHyperoxiaA1 overexpressionBcl-2 proteinMiceCell apoptosisCritical mediatorInjuryNecrosisInhibition 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
2004
Activation of the STAT pathway in acute lung injury
Severgnini M, Takahashi S, Rozo LM, Homer RJ, Kuhn C, Jhung JW, Perides G, Steer M, Hassoun PM, Fanburg BL, Cochran BH, Simon AR. Activation of the STAT pathway in acute lung injury. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2004, 286: l1282-l1292. PMID: 14729509, DOI: 10.1152/ajplung.00349.2003.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsCells, CulturedDisease Models, AnimalDNA-Binding ProteinsHydrochloric AcidInterleukin-6Janus Kinase 2KineticsLipopolysaccharidesLiverLungMaleMiceMice, Inbred BALB CMice, Inbred C57BLMitogen-Activated Protein KinasesOxidation-ReductionPancreatitisProtein-Tyrosine KinasesProto-Oncogene ProteinsRespiratory Distress SyndromeRespiratory MucosaSrc-Family KinasesSTAT3 Transcription FactorTrans-ActivatorsTumor Necrosis Factor-alphaConceptsAcute lung injuryIL-6Lung injuryLPS treatmentDevastating clinical problemGastric acid aspirationIntranasal LPS administrationResident lung cellsSTAT3 activationAcute pancreatitis modelSTAT activationAcid aspirationLPS administrationCytokine responsesInflammatory cellsInflammatory responsePancreatitis modelClinical problemMultiple organsLungLung cellsLPSEndothelial cellsTranscription factorsCritical mediator
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 lymphocytes
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 response
1998
Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation.
Waxman AB, Einarsson O, Seres T, Knickelbein RG, Warshaw JB, Johnston R, Homer RJ, Elias JA. Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation. Journal Of Clinical Investigation 1998, 101: 1970-1982. PMID: 9576762, PMCID: PMC508784, DOI: 10.1172/jci1337.Peer-Reviewed Original ResearchConceptsIL-11Lung injuryTransgene (-) animalsIL-1Alveolar-capillary protein leakPulmonary neutrophil recruitmentAcute lung injuryHyperoxic gas mixtureDNA fragmentationLevels of totalMurine toleranceLung expressionNeutrophil recruitmentProtein leakTNF productionLung antioxidantsTransgenic miceCopper-zinc superoxide dismutaseZinc superoxide dismutaseHyperoxiaGlutathione peroxidaseLipid peroxidationInjuryOxygen toxicityDismutase activity