2023
Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells.
Schupp J, Manning E, Chioccioli M, Kamp J, Christian L, Ryu C, Herzog E, Kühnel M, Prasse A, Kaminski N, Jonigk D, Homer R, Neubert L, Ius F, stringJustet A, Hariri L, Seeliger B, Welte T, Knipe R, Gottlieb J. Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 819-822. PMID: 37552025, PMCID: PMC10563189, DOI: 10.1164/rccm.202303-0544le.Peer-Reviewed Original Researchα1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis
Ishikawa G, Peng X, McGovern J, Woo S, Perry C, Liu A, Yu S, Ghincea A, Kishchanka A, Fiorini V, Hu B, Sun Y, Sun H, Ryu C, Herzog E. α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2023, 324: l639-l651. PMID: 36648147, PMCID: PMC10110730, DOI: 10.1152/ajplung.00119.2022.Peer-Reviewed Original ResearchConceptsAdrenergic nerve supplyIdiopathic pulmonary fibrosisΑ1 adrenoreceptorsPulmonary fibrosisNerve supplyCultured normal human lung fibroblastsInnate immune ligandsLung fibrosis modelNormal human lung fibroblastsSmooth muscle actinHuman lung fibroblastsAdrenal resectionAdrenoreceptor antagonismExtracellular mtDNAIPF cohortImproved survivalΑ1-adrenoreceptor antagonistsLung fibrosisAdrenal sourceFibroblast accumulationAdrenoreceptor antagonistBleomycin modelFibrosis modelLung fibrogenesisMouse model
2019
GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance
Luan HH, Wang A, Hilliard B, Carvalho F, Rosen CE, Ahasic A, Herzog E, Kang I, Pisani MA, Yu S, Zhang C, Ring A, Young L, Medzhitov R. GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance. Cell 2019, 178: 1231-1244.e11. PMID: 31402172, PMCID: PMC6863354, DOI: 10.1016/j.cell.2019.07.033.Peer-Reviewed Original ResearchConceptsViral infectionTriglyceride metabolismImpaired cardiac functionRole of GDF15Differentiation factor 15Plasma triglyceride levelsSympathetic outflowInflammatory damageTriglyceride levelsCardiac functionInflammatory responseExogenous administrationProtective effectFactor 15GDF15Central mediatorTissue toleranceBody temperatureInfectionMetabolismSepsisInflammationAdministrationHormonePlasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insights
2017
Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo e Drigo R, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature Medicine 2017, 24: 39-49. PMID: 29200204, PMCID: PMC5760280, DOI: 10.1038/nm.4447.Peer-Reviewed Original ResearchExtracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis
Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G. Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsExtracellular mitochondrial DNABronchoalveolar lavageIPF fibroblastsPulmonary fibrosisInnate immune ligandsEvent-free survivalSmooth muscle actin expressionMtDNA concentrationsSmooth muscle actin-expressing myofibroblastsGrowth factor-β1Muscle actin expressionHuman lung fibroblastsTGF-β1 stimulationExtracellular mtDNAIPF cohortClinical outcomesControl subjectsDisease progressionGlycolytic reprogrammingSoluble mediatorsTGF-β1Factor-β1Immune ligands
2014
Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective role
2013
Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials
Saketkoo L, Mittoo S, Huscher D, Khanna D, Dellaripa P, Distler O, Flaherty K, Frankel S, Oddis C, Denton C, Fischer A, Kowal-Bielecka O, LeSage D, Merkel P, Phillips K, Pittrow D, Swigris J, Antoniou K, Baughman R, Castelino F, Christmann R, Christopher-Stine L, Collard H, Cottin V, Danoff S, Highland K, Hummers L, Shah A, Kim D, Lynch D, Miller F, Proudman S, Richeldi L, Ryu J, Sandorfi N, Sarver C, Wells A, Strand V, Matteson E, Brown K, Seibold J, Aggarwal* R, Ainslie G, Alkassab F, Allanore Y, Descartes P, Anderson M, Andonopoulos A, Antin-Ozerkis D, Arrobas A, Ascherman* D, Assassi S, Baron M, Bathon* J, Behr J, Beretta L, Bingham C, Binnie M, Birring S, Boin F, Bongartz* T, Bourdin A, Bouros D, Brasington R, Bresser P, Buch M, Burge P, Carmona L, Carreira P, Carvalho C, Catoggio L, Chan K, Chapman J, Chatterjee S, Chua* F, Chung L, Conron M, Corte T, Cosgrove G, Costabel U, Cox G, Crestani B, Crofford L, Csuka M, Curbelo P, László C, Daniil Z, D'Arsigny C, Davis G, de Andrade J, De Vuyst P, Dempsey O, Derk C, Distler J, Dixon* W, Downey G, Doyle M, Drent M, Durairaj L, Emery P, Espinoza L, Farge D, Fathi M, Fell C, Fessler B, Fitzgerald J, Fox G, Foeldvari I, Frech T, Freitas S, Furst* D, Gabrielli A, García-Vicuña R, Georgiev O, Gerbino A, Gillisen A, Gladman D, Glassberg M, Gochuico B, Gogali A, Goh* N, Goldberg A, Goldberg H, Gourley* M, Griffing L, Grutters J, Gunnarsson R, Hachulla E, Hall F, Harari S, Herrick A, Herzog E, Hesselstrand R, Hirani N, Hodgson U, Hollingsworth H, Homer R, Hoyles R, Hsu V, Hubbard R, Hunzelmann N, Isasi M, Isasi E, Jimenez J, Johnson S, Jones C, Kahaleh B, Kairalla R, Kalluri M, Kalra S, Kaner R, Kinder B, Klingsberg R, Kokosi M, Kolb M, Kur-Zalewska J, Kuwana* M, Lake F, Lally E, Lasky J, Laurindo I, Able L, Lee P, Leonard C, Lien D, Limper A, Liossis S, Lohr K, Loyd J, Lundberg* I, Mageto Y, Maher T, Mahmud T, Manganas H, Marie I, Marras T, Martinez J, Martinez F, Mathieu A, Matucci-Cerinic* M, Mayes* M, McKown K, Medsger T, Meehan R, Cristina M, Meyer K, Millar A, Moğulkoç N, Molitor J, Morais A, Mouthon P, Müller V, Müller-Quernheim J, Nadashkevich O, Nador R, Nash P, Nathan S, Navarro C, Neves S, Noth I, Nunes H, Olson A, Opitz C, Padilla M, Pappas D, Parfrey H, Pego-Reigosa J, Pereira C, Perez R, Pope* J, Porter J, Renzoni E, Riemekasten G, Riley D, Rischmueller M, Rodriguez-Reyna T, Rojas-Serrano, Romam J, Rosen G, Rossman M, Rothfield N, Sahn S, Sanduzzi A, Scholand M, Selman M, Senécal J, Seo P, Silver* R, Solomon J, Steen* V, Stevens W, Strange C, Sussman R, Sutton E, Sweiss N, Tornling G, Tzelepis G, Undurraga A, Vacca A, Vancheri C, Varga J, Veale D, Volkov S, Walker U, Wencel M, Wesselius L, Wickremasinghe M, Wilcox P, Wilsher M, Wollheim F, Wuyts W, Yung G, Zanon P, Zappala C, Groshong S, Leslie K, Myers J, Padera R, Desai S, Goldin J, Kazerooni E, Klein J, Lynch D, Keen K. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials. Thorax 2013, 69: 436. PMID: 24368713, PMCID: PMC3995282, DOI: 10.1136/thoraxjnl-2013-204202.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisConnective tissue diseaseInterstitial lung diseaseCTD-ILDPulmonary fibrosisTissue diseaseLung diseaseClinical trialsOutcome measuresRelated interstitial lung diseaseNominal group panelHealth-related qualityPatient focus groupsMulticentre clinical trialAppropriate outcome measuresClinical trial designILD expertsDisease activityMulticentre RCTsTreatment responseLung physiologyTrial designConsensus methodologyIdentification of outcomesLung imaging
2010
TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P
Murray LA, Chen Q, Kramer MS, Hesson DP, Argentieri RL, Peng X, Gulati M, Homer RJ, Russell T, van Rooijen N, Elias JA, Hogaboam CM, Herzog EL. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. The International Journal Of Biochemistry & Cell Biology 2010, 43: 154-162. PMID: 21044893, DOI: 10.1016/j.biocel.2010.10.013.Peer-Reviewed Original ResearchConceptsSerum amyloid PAnti-fibrotic effectsLung fibrosisFibrocyte accumulationAmyloid PAberrant extracellular matrix (ECM) depositionTransgenic mouse modelM2 macrophage differentiationPleiotropic growth factorExtracellular matrix depositionAirway inflammationIPF patientsAirway remodelingPulmonary fibrosisMacrophage accumulationLung diseaseLiposomal clodronateCXCL10 expressionM2 macrophagesMonocyte responsePulmonary macrophagesMouse modelCollagen depositionPathogenic mechanismsDisease severityTissue-Engineered Lungs for in Vivo Implantation
Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE. Tissue-Engineered Lungs for in Vivo Implantation. Science 2010, 329: 538-541. PMID: 20576850, PMCID: PMC3640463, DOI: 10.1126/science.1189345.Peer-Reviewed Original ResearchConceptsLung tissueLung matrixAcellular lung matrixNative lung tissueTissue-engineered lungsLung transplantationPrimary therapyAdult lung tissueAdult ratsPulmonary epitheliumVascular endotheliumFunctional lungLung regenerationVascular compartmentLungSeeded endothelial cellsMechanical characteristicsEndothelial cellsVivo implantationRatsEpitheliumTissueCellular componentsExtracellular matrixGas exchangeCirculating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype
Mathai SK, Gulati M, Peng X, Russell TR, Shaw AC, Rubinowitz AN, Murray LA, Siner JM, Antin-Ozerkis DE, Montgomery RR, Reilkoff RA, Bucala RJ, Herzog EL. Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype. Laboratory Investigation 2010, 90: 812-823. PMID: 20404807, PMCID: PMC3682419, DOI: 10.1038/labinvest.2010.73.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseSSc-ILD patientsSSc-ILDIL-10Normal controlsProfibrotic cellsSystemic sclerosisLung diseaseCollagen-producing cellsMCP-1Profibrotic phenotypeSSc-related interstitial lung diseaseFlow cytometryPeripheral blood profilesSSc-ILD cohortsIL-10 secretionSystemic sclerosis patientsExpression of CD163Blood of patientsHealthy aged controlsCultured CD14Profibrotic characteristicsProfibrotic mediatorsTNF levelsSclerosis patients