2019
Plasma 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
2024
INTERACTIONS BETWEEN MITOCHONDRIAL DNA AND TOLL-LIKE RECEPTOR 9 MEDIATES PULMONARY FIBROSIS
LEE C, TRUJILLO G, REGUEIRO-REN A, LIU C, HU B, SUN Y, KHOURY J, KHOURY J, AHANGARI F, ISHIKAWA G, WALIA A, PIVARNIK T, YU S, WOO S, FIORINI V, MCGOVERN J, AL JUMAILY K, SUN H, PENG X, ANTIN-OZERKIS D, SAULER M, KAMINSKI N, HERZOG E. INTERACTIONS BETWEEN MITOCHONDRIAL DNA AND TOLL-LIKE RECEPTOR 9 MEDIATES PULMONARY FIBROSIS. CHEST Journal 2024, 166: a3384-a3386. DOI: 10.1016/j.chest.2024.06.2020.Peer-Reviewed Original ResearchANTAGONISM OF CGAS ABROGATES INFLAMMATORY FIBROTIC RESPONSES IN TRANSLATIONAL MODELS OF SCLERODERMA-ASSOCIATED INTERSTITIAL LUNG DISEASE
YU S, LEE C, HU B, SUN Y, SHAO S, SUN H, GHINCEA A, WOO S, MCGOVERN J, SABER T, GUNES B, KUJAWSKI S, PEREZ S, ODELL W, HINCHCLIFF M, VARGA J, SAULER M, GOMEZ J, RYU C, HERZOG E. ANTAGONISM OF CGAS ABROGATES INFLAMMATORY FIBROTIC RESPONSES IN TRANSLATIONAL MODELS OF SCLERODERMA-ASSOCIATED INTERSTITIAL LUNG DISEASE. CHEST Journal 2024, 166: a3380-a3381. DOI: 10.1016/j.chest.2024.06.2018.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 modelPlasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts
Sand J, Jessen H, Leeming D, Yu S, Lee C, Hu B, Sun Y, Adams T, Pivarnik T, Liu A, Woo S, McGovern J, Fiorini V, Saber T, Higuero-Sevilla J, Gulati M, Kaminski N, Damsky W, Shaw A, Mohanty S, Goobie G, Zhang Y, Herzog E, Ryu C. Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts. Thorax 2024, 79: thorax-2023-221095. PMID: 39117421, DOI: 10.1136/thorax-2023-221095.Peer-Reviewed Original ResearchSarcoidosis cohortMultiorgan diseasePRO-C3Interleukin-4Case Control Etiologic Study of SarcoidosisPlasma levels of interleukin-4Alpha-1 antitrypsin deficiencyLevels of interleukin-4Pathogenesis of sarcoidosisC6MC3MHealthy control patientsStudy of sarcoidosisGenomic researchAbnormal extracellular matrixAssociated with dermatological diseaseCollagen degradationScadding stageCorticosteroid useComplex diseasesPRO-C6Control patientsIL-13IL-5IL-9
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 populationα1 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
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