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
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMice
2011
RIG-like Helicase Innate Immunity Inhibits Vascular Endothelial Growth Factor Tissue Responses via a Type I IFN–dependent Mechanism
Ma B, Dela Cruz CS, Hartl D, Kang MJ, Takyar S, Homer RJ, Lee CG, Elias JA. RIG-like Helicase Innate Immunity Inhibits Vascular Endothelial Growth Factor Tissue Responses via a Type I IFN–dependent Mechanism. American Journal Of Respiratory And Critical Care Medicine 2011, 183: 1322-1335. PMID: 21278304, PMCID: PMC3114061, DOI: 10.1164/rccm.201008-1276oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDEAD Box Protein 58DEAD-box RNA HelicasesDisease Models, AnimalEdemaFocal Adhesion Protein-Tyrosine KinasesImmunity, InnateInflammationInterferon Type IMiceMice, TransgenicMitogen-Activated Protein KinasesNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasePoly I-CPulmonary Disease, Chronic ObstructiveToll-Like Receptor 3Vascular Endothelial Growth Factor AConceptsVascular endothelial growth factorType 2 inflammationChronic obstructive pulmonary disease exacerbationsObstructive pulmonary disease exacerbationsChronic obstructive pulmonary diseaseViral pathogen-associated molecular patternsEndothelial nitric oxide synthaseRIG-like helicasePulmonary disease exacerbationsObstructive pulmonary diseasePathogenesis of asthmaRespiratory syncytial virusNormal pulmonary physiologyNitric oxide synthaseAntiviral innate immunityPathogen-associated molecular patternsReceptor-dependent pathwayTissue responseEndothelial growth factorVEGF receptor 1Ability of VEGFDisease exacerbationPulmonary diseaseRespiratory virusesControl mice
2010
Recent advances in pulmonary fibrosis: implications for scleroderma
Homer RJ, Herzog EL. Recent advances in pulmonary fibrosis: implications for scleroderma. Current Opinion In Rheumatology 2010, 22: 683-689. PMID: 20693906, DOI: 10.1097/bor.0b013e32833ddcc9.BooksConceptsPulmonary fibrosisEpithelial cell injuryCell injuryIdiopathic pulmonary fibrosisRole of lymphocytesAlternative macrophage activationPathogenesis of sclerodermaTranslational human studiesEpithelial-mesenchymal transitionEndoplasmic reticulum stressMost patientsSystemic sclerosisLung fibrosisLymphocyte functionEffective therapyLeading causeLung parenchymaFibrotic responseHuman studiesMacrophage activationScar tissueFibrosisPossible associationAnimal modelingPatientsRole of Breast Regression Protein–39 in the Pathogenesis of Cigarette Smoke–Induced Inflammation and Emphysema
Matsuura H, Hartl D, Kang MJ, Dela Cruz CS, Koller B, Chupp GL, Homer RJ, Zhou Y, Cho WK, Elias JA, Lee CG. Role of Breast Regression Protein–39 in the Pathogenesis of Cigarette Smoke–Induced Inflammation and Emphysema. American Journal Of Respiratory Cell And Molecular Biology 2010, 44: 777-786. PMID: 20656949, PMCID: PMC3135840, DOI: 10.1165/rcmb.2010-0081oc.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseBRP-39/YKLBreast regression protein 39YKL-40BRP-39Alveolar destructionCigarette smokeChitinase-like protein YKL-40Emphysematous alveolar destructionLungs of CSObstructive pulmonary diseaseProtein YKL-40Excessive inflammatory responseAirway epithelial cellsAlveolar type II cellsNull mutant miceProtein 39Epithelial cell apoptosisType II cellsCurrent smokersPulmonary diseaseBronchoalveolar lavageTissue inflammationEmphysematous destructionSerum concentrations
2009
Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation
Niu N, Laufer T, Homer RJ, Cohn L. Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation. The Journal Of Immunology 2009, 183: 1523-1527. PMID: 19596982, DOI: 10.4049/jimmunol.0901349.Peer-Reviewed Original ResearchConceptsAllergic airway inflammationMHC class II expressionAirway inflammationDendritic cellsClass II expressionTh2 generationTh2 immunityTh2-dependent allergic airway inflammationTh1 immune responseIFN-gamma productionAirway neutrophiliaTh2 primingRespiratory tractTh2 cellsImmune responseClass II signalsInflammationTh2 recruitmentMice resultsMiceCells altersImmunityActivationCellsNeutrophiliaA sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma
Caceres AI, Brackmann M, Elia MD, Bessac BF, del Camino D, D'Amours M, Witek JS, Fanger CM, Chong JA, Hayward NJ, Homer RJ, Cohn L, Huang X, Moran MM, Jordt SE. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 9099-9104. PMID: 19458046, PMCID: PMC2684498, DOI: 10.1073/pnas.0900591106.Peer-Reviewed Original ResearchConceptsAsthmatic airway inflammationAirway inflammationAirway hyperreactivityAllergen challengeHC-030031Airway allergen challengeEndogenous TRPA1 agonistsMurine ovalbumin modelImpaired inflammatory responseTreatment of asthmaRole of TRPA1Wild-type miceAirway epithelial functionAllergic inflammatory conditionsPromising pharmacological targetNeuronal ion channelsLipid peroxidation productsIon channelsAllergic asthmaAirway exposureEosinophil infiltrationLeukocyte infiltrationContractile stimuliInflammatory disordersOvalbumin modelRole 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
Acidic Mammalian Chitinase Is Secreted via an ADAM17/Epidermal Growth Factor Receptor-dependent Pathway and Stimulates Chemokine Production by Pulmonary Epithelial Cells*
Hartl D, He CH, Koller B, Da Silva CA, Homer R, Lee CG, Elias JA. Acidic Mammalian Chitinase Is Secreted via an ADAM17/Epidermal Growth Factor Receptor-dependent Pathway and Stimulates Chemokine Production by Pulmonary Epithelial Cells*. Journal Of Biological Chemistry 2008, 283: 33472-33482. PMID: 18824549, PMCID: PMC2586247, DOI: 10.1074/jbc.m805574200.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorLung epithelial cellsAcidic mammalian chitinaseChemokine productionEpithelial cellsT helper cell type 2 inflammationEpidermal growth factor receptor-dependent pathwayAsthma-like responsesType 2 inflammationMammalian chitinaseEpithelial cell productionReceptor-dependent pathwayPulmonary epithelial cellsEGFR-dependent pathwayGrowth factor receptorCotransfection experimentsEffector responsesParacrine fashionEGFR inhibitionSecretionFactor receptorA549 cellsAMCaseRecombinant AMCaseRegulatory effectsEndogenous 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 lung
2007
Inhibition of NF-κB Activation Reduces the Tissue Effects of Transgenic IL-13
Chapoval SP, Al-Garawi A, Lora JM, Strickland I, Ma B, Lee PJ, Homer RJ, Ghosh S, Coyle AJ, Elias JA. Inhibition of NF-κB Activation Reduces the Tissue Effects of Transgenic IL-13. The Journal Of Immunology 2007, 179: 7030-7041. PMID: 17982094, DOI: 10.4049/jimmunol.179.10.7030.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsApoptosisCaspasesHeterocyclic Compounds, 3-RingI-kappa B KinaseInflammationInhibitor of Apoptosis ProteinsInterleukin-13MiceMice, Mutant StrainsMice, TransgenicMucusNF-kappa B p50 SubunitPeptidesPulmonary AlveoliPulmonary FibrosisPyridinesReceptors, Cell SurfaceRespiratory HypersensitivitySignal TransductionTh2 CellsConceptsTransgenic IL-13IL-13Alveolar remodelingIL-13 transgenic miceNF-kappaBMajor Th2 cytokinesExcessive mucus productionTissue effectsNF-κB activationNF-kappaB activationNF-kappaB activityNF-kappaB componentsAirway hyperresponsivenessTh2 cytokinesTissue inflammationPharmacologic approachesMucus productionIL-13Ralpha1Murine lungSmall molecule inhibitorsTissue alterationsNF-kappaB.MiceCell apoptosisDiminished levelsP21 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 inhibitorsAirway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma
Simeone-Penney MC, Severgnini M, Tu P, Homer RJ, Mariani TJ, Cohn L, Simon AR. Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma. The Journal Of Immunology 2007, 178: 6191-6199. PMID: 17475846, DOI: 10.4049/jimmunol.178.10.6191.Peer-Reviewed Original ResearchConceptsHouse dust miteAirway epitheliumAllergic inflammationRole of STAT3Murine modelNovel asthma therapiesSignificant decreaseSTAT3 activationTh2 cell recruitmentAcute phase responseWild-type animalsAirway hyperresponsivenessAirway eosinophiliaAirway inflammationAllergic asthmaAsthma therapyChronic asthmaLung inflammationC57BL/6 miceAllergic responsesDust miteEpithelial STAT3Immune cellsSmooth muscleSTAT3 transcription factorIncreased 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-11A Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract
Niu N, Le Goff MK, Li F, Rahman M, Homer RJ, Cohn L. A Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract. The Journal Of Immunology 2007, 178: 3846-3855. PMID: 17339484, DOI: 10.4049/jimmunol.178.6.3846.Peer-Reviewed Original ResearchConceptsAirway inflammationInflammatory diseasesRespiratory tractTh2-induced airway inflammationChronic airway inflammatory diseaseLymphocyte-deficient miceState of immunosuppressionAcute airway inflammationAirway inflammatory diseasesEffector Th cellsTh2 cells resultsAirway hyperresponsivenessInflammation wanesTh2 modelEffector Th1Respiratory illnessTh cellsInhalational exposureInflammationInhibitory effectSuch diseasesDiseaseStriking inhibitionTh1Localized treatmentIL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation
Kang MJ, Homer RJ, Gallo A, Lee CG, Crothers KA, Cho SJ, Rochester C, Cain H, Chupp G, Yoon HJ, Elias JA. IL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation. The Journal Of Immunology 2007, 178: 1948-1959. PMID: 17237446, DOI: 10.4049/jimmunol.178.3.1948.Peer-Reviewed Original ResearchConceptsChronic obstructive lung diseaseObstructive lung diseaseIL-18Wild-type miceCigarette smokeLung diseasePulmonary emphysemaIL-18RalphaPathogenesis of CSEffects of CSAir-exposed miceIL-18 pathwayIL-18 receptor αIL-18R signalingTh1 inflammationPulmonary macrophagesEpithelial apoptosisReceptor αInflammationPotent stimulatorEmphysemaCaspase-1MiceCritical roleElevated levelsTransforming Growth Factor (TGF)-β1 Stimulates Pulmonary Fibrosis and Inflammation via a Bax-dependent, Bid-activated Pathway That Involves Matrix Metalloproteinase-12*
Kang HR, Cho SJ, Lee CG, Homer RJ, Elias JA. Transforming Growth Factor (TGF)-β1 Stimulates Pulmonary Fibrosis and Inflammation via a Bax-dependent, Bid-activated Pathway That Involves Matrix Metalloproteinase-12*. Journal Of Biological Chemistry 2007, 282: 7723-7732. PMID: 17209037, DOI: 10.1074/jbc.m610764200.Peer-Reviewed Original ResearchConceptsMMP-12Pulmonary fibrosisWild typeGrowth factorInterstitial lung diseaseEffects of TGFMatrix metalloproteinase-12Pulmonary diseaseExaggerated productionPulmonary responseLung diseaseMMP-9Effector functionsTIMP-1Matrix metalloproteinaseFibrosisPotent stimulatorMetalloproteinase-12TGFBax activationInflammationPathogenesisBaxApoptosisDisease
2006
Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling
Shim YM, Zhu Z, Zheng T, Lee CG, Homer RJ, Ma B, Elias JA. Role of 5-Lipoxygenase in IL-13-Induced Pulmonary Inflammation and Remodeling. The Journal Of Immunology 2006, 177: 1918-1924. PMID: 16849505, DOI: 10.4049/jimmunol.177.3.1918.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArachidonate 5-LipoxygenaseChronic DiseaseDinoprostoneInflammationInterleukin-13LeukotrienesLungMatrix Metalloproteinase 12MetalloendopeptidasesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPulmonary AlveoliPulmonary FibrosisSignal TransductionTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsIL-13-induced inflammationIL-13Transgenic IL-13Activation of TGFMatrix metalloproteinase-12Th2 inflammationPulmonary inflammationC57BL/6 miceChronic inflammationCysteinyl LTsFibrotic responseLevels of mRNATissue fibrosisLT metabolismInflammationAlveolar remodelingReceptor 1Metalloproteinase-12Pathway activationExaggerated levelsOptimal stimulationCytosolic phospholipasePathogenesisActivation pathwayRemodelingEssential role of nitric oxide in VEGF-induced, asthma-like angiogenic, inflammatory, mucus, and physiologic responses in the lung
Bhandari V, Choo-Wing R, Chapoval SP, Lee CG, Tang C, Kim YK, Ma B, Baluk P, Lin MI, McDonald DM, Homer RJ, Sessa WC, Elias JA. Essential role of nitric oxide in VEGF-induced, asthma-like angiogenic, inflammatory, mucus, and physiologic responses in the lung. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 11021-11026. PMID: 16832062, PMCID: PMC1544167, DOI: 10.1073/pnas.0601057103.Peer-Reviewed Original ResearchConceptsInducible NOSNitric oxideEndothelial NOS inhibitorDendritic cell activationNO-dependent mechanismAirway hyperresponsivenessMucus metaplasiaLymphocyte accumulationPulmonary alterationsCell hyperplasiaNOS inhibitorNormal micePhysiologic responsesCell activationInflammationENOSVEGFMiceIndependent mechanismsTissue responseLatter responseLungAngiogenesisRemodelingNull mutationAdenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis
Ma B, Blackburn MR, Lee CG, Homer RJ, Liu W, Flavell RA, Boyden L, Lifton RP, Sun CX, Young HW, Elias JA. Adenosine metabolism and murine strain–specific IL-4–induced inflammation, emphysema, and fibrosis. Journal Of Clinical Investigation 2006, 116: 1274-1283. PMID: 16670768, PMCID: PMC1451205, DOI: 10.1172/jci26372.Peer-Reviewed Original ResearchConceptsIL-4C57BL/6 miceBALB/cAirway fibrosisEosinophilic inflammationAdenosine metabolismEmphysematous alveolar destructionTissue adenosine levelsAdenosine receptor expressionIL-4 inducesAdenosine deaminase activityAlveolar destructionTh1 cytokinesC57BL/6 animalsEmphysematous destructionAdenosine levelsReceptor expressionTg animalsMurine lungMetalloproteinase-2Alveolar remodelingTissue inhibitorFibrosisInflammationPremature death