2024
The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice
McGovern J, Perry C, Ghincea A, Herzog E, Shao S, Sun H. The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024 PMID: 39470613, DOI: 10.1152/ajplung.00062.2024.Peer-Reviewed Original ResearchLung fibrosisSurgical adrenalectomyBronchoalveolar lavageLung tissueBleomycin-induced pulmonary fibrosisAlpha-smooth muscle actinModel of lung fibrosisBleomycin model of lung fibrosisProgressive lung fibrosisLimited treatment optionsSmooth muscle actinWild type miceEffects of adrenalectomyProduction of catecholaminesDecrease of lymphocytesAdrenal ablationAldosterone levelsBleomycin administrationBleomycin modelSham surgeryAld levelsLung remodelingPulmonary fibrosisType miceAdrenal glandRetraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee C, He C, Park J, Lee J, Kamle S, Ma B, Akosman B, Cortez R, Chen E, Zhou Y, Herzog E, Ryu C, Peng X, Rosas I, Poli S, Bostwick C, Choi A, Elias J, Lee C. Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2024, 7: e202402987. PMID: 39209538, PMCID: PMC11361373, DOI: 10.26508/lsa.202402987.Peer-Reviewed Original ResearchToll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.
Trujillo G, Regueiro-Ren A, Liu C, Hu B, Sun Y, Ahangari F, Fiorini V, Ishikawa G, Al Jumaily K, Khoury J, McGovern J, Lee C, Peng X, Pivarnik T, Sun H, Walia A, Woo S, Yu S, Antin-Ozerkis D, Sauler M, Kaminski N, Herzog E, Ryu C. Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024 PMID: 39189851, DOI: 10.1164/rccm.202401-0065oc.Peer-Reviewed Original ResearchToll-like receptor 9Model of pulmonary fibrosisIdiopathic pulmonary fibrosisPulmonary fibrosisFibroproliferative responseLung diseaseIdiopathic pulmonary fibrosis cohortsExpression of toll-like receptor 9Toll-like receptor 9 activationTransplant-free survivalExpression of MCP-1Cohort of patientsSlow clinical progressionFibrotic lung diseaseAccelerated disease courseFatal lung diseaseIP-10Pharmacodynamic endpointsPreclinical modelsDisease courseClinical progressionPlasma mtDNAMCP-1Receptor 9Mouse modelSingle-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Unterman A, Zhao A, Neumark N, Schupp J, Ahangari F, Cosme C, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida T, Gomez J, Herazo-Maya J, Dela Cruz C, Herzog E, Kaminski N. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 484-496. PMID: 38717443, PMCID: PMC11351796, DOI: 10.1164/rccm.202306-0979oc.Peer-Reviewed Original ResearchStable idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsProgressive idiopathic pulmonary fibrosisPeripheral immune systemT cellsPulmonary fibrosisCohort of IPF patientsAssociated with decreased survivalIdiopathic pulmonary fibrosis patientsPeripheral blood mononuclear cell samplesPeripheral blood cell populationsImmune systemFraction of TregsRegulatory T cellsBlood mononuclear cellsBlood cell populationsFlow cytometry analysisImmune aberrationsIPF patientsTregsMononuclear cellsSingle-cell RNA sequencingLung homogenatesMonocyte chemoattractantSingle-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nikola F, Flint J, Yan X, Adams T, Justet A, Sumida T, Zhao J, Schupp J, Raredon M, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling A, Prasse A, Ryu C, Herzog E, Selman M, Pardo A, Kaminski N. Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 1252-1266. PMID: 38924775, PMCID: PMC11568434, DOI: 10.1164/rccm.202401-0078oc.Peer-Reviewed Original ResearchFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBronchoalveolar lavage cellsBlood mononuclear cellsClassical monocytesHypersensitivity pneumonitisPulmonary fibrosisT cellsImmune perturbationsLavage cellsMononuclear cellsCD8+ T cellsCytotoxic T cellsInterstitial lung diseaseHypersensitivity pneumonitis patientsCytotoxic CD4Immune aberrationsPneumonic patientsPneumonitisLung diseaseHealthy controlsImmune mechanismsPatient cellsSingle-cell transcriptomicsAlveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF
Kim S, Nouws J, Cooley J, Ahangari F, Leng L, Elias J, Kaminski N, Lee P, Redente E, Kang M, Sun H, Herzog E, Bucala R, Prasse A, Sauler M. Alveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF. 2024, a3001-a3001. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a3001.Peer-Reviewed Original Research
2023
Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts
Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster S, Pivarnik T, Khan Z, Adams T, Herzog E, Kaminski N, Gulati M, Ryu C. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts. CHEST Journal 2023, 165: 1174-1185. PMID: 37977267, PMCID: PMC11110677, DOI: 10.1016/j.chest.2023.11.020.Peer-Reviewed Original ResearchPatient-related outcome measuresToll-like receptor 9Fatigue Assessment ScalePlasma mtDNA concentrationsTLR9 activationSarcoidosis patientsMtDNA concentrationsMulti-organ sarcoidosisCommon chief complaintInnate immune activationNovel therapeutic strategiesDomains of fatigueSevere clinical phenotypePsychobiologic mechanismsSarcoidosis cohortScadding stageCorticosteroid useCytokine levelsExtrapulmonary diseaseProspective cohortFAS scoresPulmonary fibrosisChief complaintImmune activationPatient populationCorrection: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee C, He C, Park J, Lee J, Kamle S, Ma B, Akosman B, Cotez R, Chen E, Zhou Y, Herzog E, Ryu C, Peng X, Rosas I, Poli S, Bostwick C, Choi A, Elias J, Lee C. Correction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2023, 6: e202302065. PMID: 37037591, PMCID: PMC10088146, DOI: 10.26508/lsa.202302065.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
2022
Ameliorating Fibrosis in Murine and Human Tissues with END55, an Endostatin-Derived Fusion Protein Made in Plants
Mlakar L, Garrett S, Watanabe T, Sanderson M, Nishimoto T, Heywood J, Helke K, Pilewski J, Herzog E, Feghali-Bostwick C. Ameliorating Fibrosis in Murine and Human Tissues with END55, an Endostatin-Derived Fusion Protein Made in Plants. Biomedicines 2022, 10: 2861. PMID: 36359382, PMCID: PMC9687961, DOI: 10.3390/biomedicines10112861.Peer-Reviewed Original ResearchAnti-fibrotic effectsIdiopathic pulmonary fibrosisSystemic sclerosisPulmonary fibrosisLung fibrosisMouse modelSignificant anti-fibrotic effectEffective anti-fibrotic therapiesBleomycin mouse modelLungs of patientsAnti-fibrotic therapiesPrevention of skinSecond mouse modelCollagen XVIII/endostatinGrowth factor-β1Matrix-degrading enzymesLung transplantationSignificant morbidityHuman tissuesLung diseaseHealth burdenEffective treatmentFactor-β1Organ fibrosisFibrosisAdaptive Immunity in Interstitial Lung Disease
Winkler J, Herzog E. Adaptive Immunity in Interstitial Lung Disease. 2022, 144-157. DOI: 10.1016/b978-0-08-102723-3.00018-4.ChaptersInterstitial lung diseaseIdiopathic pulmonary fibrosisLung diseaseAdaptive immunityBasic science investigationsAutoimmune conditionsPulmonary fibrosisHumoral responseClinical observationsTranslational studiesAberrant remodelingDiseaseUnifying hypothesisImmunityUnanswered questionsImmunopathogenesisSclerodermaFibrosisInjury
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 ResearchConceptsThyroid hormonesMitochondrial functionPulmonary fibrosisLung fibrosisLung epitheliumFibrosisMiceHormoneEpitheliumExtracellular 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 rolePulmonary Fibrosis
Murray L, Homer R, Gulati M, Herzog E. Pulmonary Fibrosis. 2014, 2636-2653. DOI: 10.1016/b978-0-12-386456-7.05307-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInterstitial lung diseasePulmonary fibrosisLung fibrosisConnective tissue disease-related interstitial lung diseaseIdiopathic pulmonary fibrosisSalient clinical featuresDistinctive pathological featuresWound healing responseClinical featuresChronic injuryLung diseasePathological featuresCirculating BiomarkersInflammatory responseLung parenchymaCertain therapiesPathogenic mechanismsScar tissueClinical monitoringFibrosisHealing responseFatal natureGenetic formsDiseasePotential 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 severity