2013
Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway
Choo-Wing R, Syed MA, Harijith A, Bowen B, Pryhuber G, Janér C, Andersson S, Homer RJ, Bhandari V. Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway. American Journal Of Respiratory Cell And Molecular Biology 2013, 48: 749-757. PMID: 23470621, PMCID: PMC3727872, DOI: 10.1165/rcmb.2012-0381oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBronchopulmonary DysplasiaCelecoxibCell DeathCyclooxygenase 2Cyclooxygenase 2 InhibitorsEndoplasmic Reticulum StressHumansHyperoxiaImmunohistochemistryInfant, NewbornInterferon-gammaLungMiceMice, Inbred C57BLMice, TransgenicPyrazolesRNA, Small InterferingSulfonamidesTranscription Factor CHOPConceptsBronchopulmonary dysplasiaCyclooxygenase-2Endoplasmic reticulum stress-dependent pathwaysER stress pathway activationPathway mediatorsHuman bronchopulmonary dysplasiaFinal common pathwayAlveolar epithelial cellsImpaired alveolarizationStress pathway activationCOX2 inhibitionMurine modelMurine lungClinical relevanceIFNVivo modelHyperoxiaLungHuman lungPathway activationCHOP siRNAStress-dependent pathwaysInjuryEpithelial cellsCommon pathway
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 hyaluronanReceptorsHyaluronanCutting Edge: TLR4 Deficiency Confers Susceptibility to Lethal Oxidant Lung Injury
Zhang X, Shan P, Qureshi S, Homer R, Medzhitov R, Noble PW, Lee PJ. Cutting Edge: TLR4 Deficiency Confers Susceptibility to Lethal Oxidant Lung Injury. The Journal Of Immunology 2005, 175: 4834-4838. PMID: 16210584, DOI: 10.4049/jimmunol.175.8.4834.Peer-Reviewed Original ResearchConceptsTLR4-deficient miceLung injuryAntioxidant gene heme oxygenase-1Gene heme oxygenase-1Oxidant lung injuryBcl-2Heme oxygenase-1Life-sustaining measuresPhospho-Akt levelsNovel mechanistic linkRespiratory failureIll patientsLung integrityMurine modelOxygenase-1Oxidant stressProtective roleHost responseInnate immunityInjuryPhospho-AktHyperoxiaConfer susceptibilityMiceMammalian TLR4Bcl-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 mediatorInjuryNecrosisAirway Remodeling in Asthma: Therapeutic Implications of Mechanisms
Homer RJ, Elias JA. Airway Remodeling in Asthma: Therapeutic Implications of Mechanisms. Physiology 2005, 20: 28-35. PMID: 15653837, DOI: 10.1152/physiol.00035.2004.Peer-Reviewed Original ResearchInhibition 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
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