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 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 chemoattractantRole of Noradrenaline and Macrophage Dynamics in Pulmonary Fibrosis
Ishikawa G, Peng X, Mcgovern J, Ghincea A, Saber T, Sun H, Sauler M, Ryu C, Herzog E. Role of Noradrenaline and Macrophage Dynamics in Pulmonary Fibrosis. 2024, a5206-a5206. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5206.Peer-Reviewed Original Research
2023
Toll-like Receptor-9 Activation Promotes Persistent Inflammation in the Lung During Influenza Infection
Essayas H, Kim J, Mcgovern J, Peng X, Cai Y, Ishikawa G, Herzog E, Dela Cruz C, Ryu C, Sharma L. Toll-like Receptor-9 Activation Promotes Persistent Inflammation in the Lung During Influenza Infection. 2023, a5608-a5608. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a5608.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
PTX3 in Granuloma Formation and Sarcoidosis: Helping Macrophages Accept a “Complement”
Ishikawa G, Herzog EL. PTX3 in Granuloma Formation and Sarcoidosis: Helping Macrophages Accept a “Complement”. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1064-1065. PMID: 35820078, PMCID: PMC9704837, DOI: 10.1164/rccm.202207-1277ed.Commentaries, Editorials and Letters
2021
Evolving Perspectives on Innate Immune Mechanisms of IPF
Ishikawa G, Liu A, Herzog EL. Evolving Perspectives on Innate Immune Mechanisms of IPF. Frontiers In Molecular Biosciences 2021, 8: 676569. PMID: 34434962, PMCID: PMC8381017, DOI: 10.3389/fmolb.2021.676569.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisInnate immunityInnate immune populationsMolecular patternsMyeloid suppressor cellsInnate lymphoid cellsInnate immune mechanismsEpithelial-fibroblast interactionsRole of substancesSuppressor cellsPulmonary fibrosisImmune populationsImmune mechanismsDisease outcomePotential therapyLymphoid cellsHuman studiesFibrotic microenvironmentCommensal microbesAnimal modelingGenetic factorsImmunityFuture studiesComplex roleCellsElevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes
Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1137-l1146. PMID: 33851886, PMCID: PMC8285626, DOI: 10.1152/ajplung.00575.2020.Peer-Reviewed Original ResearchConceptsIL-15 concentrationsIL-15Bronchoalveolar lavageDisease pathogenesisSarcoidosis lungClinical manifestationsLineages of miceIL-15 receptor αHuman cohortsInflammation of sarcoidosisIL-15 levelsOngoing inflammatory processSystemic granulomatous diseaseNumber of granulomasDisease phenotypeSarcoidosis cohortTDM administrationGranuloma numberComorbid conditionsClinical progressionInterleukin-15Granulomatous diseaseInflammatory processGranuloma formationHealthy controlsMacrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins
2019
Shared and Tissue-Specific Expression Signatures between Bone Marrow from Primary Myelofibrosis and Essential Thrombocythemia
Ishikawa G, Fujiwara N, Hirschfield H, Varricchio L, Hoshida Y, Barosi G, Rosti V, Padilla M, Mazzarini M, Friedman SL, Hoffman R, Migliaccio AR. Shared and Tissue-Specific Expression Signatures between Bone Marrow from Primary Myelofibrosis and Essential Thrombocythemia. Experimental Hematology 2019, 79: 16-25.e3. PMID: 31678370, PMCID: PMC6910948, DOI: 10.1016/j.exphem.2019.10.001.Peer-Reviewed Original ResearchConceptsBone marrowLung fibrosisMyeloproliferative neoplasmsEssential thrombocytopeniaLiver fibrosisPhiladelphia-negative myeloproliferative neoplasmsProtein 1Possible therapeutic targetPrimary myelofibrosis patientsExpression of Id1Extracellular matrix protein 1Poor prognosisIL-8Myelofibrosis patientsEssential thrombocythemiaTherapeutic targetPrimary myelofibrosisFibrosisMegakaryocyte hyperplasiaCholesterol homeostasisBM functionHematopoietic failureMatrix protein 1K-rasPotential targetConcomitant Interstitial Lung Disease with Psoriasis
Ishikawa G, Dua S, Mathur A, Acquah SO, Salvatore M, Beasley MB, Padilla ML. Concomitant Interstitial Lung Disease with Psoriasis. Canadian Respiratory Journal 2019, 2019: 5919304. PMID: 31534591, PMCID: PMC6732645, DOI: 10.1155/2019/5919304.Peer-Reviewed Original ResearchConceptsNonspecific interstitial pneumoniaPneumonia patternConcomitant diagnosisConcomitant interstitial lung diseaseInterstitial lung disease patientsUsual interstitial pneumonia patternChronic hypersensitivity pneumonitisLung disease patientsCryptogenic organizing pneumoniaFurther prospective studiesIdiopathic pulmonary fibrosisInterstitial lung diseaseInterstitial pneumonia patternMount Sinai HospitalConcomitant psoriasisNSIP patternILD patientsImmunosuppressive therapyOrganizing pneumoniaInterstitial pneumoniaMedian ageRetrospective reviewCase seriesPulmonary fibrosisHypersensitivity pneumonitis
2018
Is It Idiopathic Pulmonary Fibrosis or Not?
Salvatore M, Ishikawa G, Padilla M. Is It Idiopathic Pulmonary Fibrosis or Not? The Journal Of The American Board Of Family Medicine 2018, 31: 151-162. PMID: 29330249, DOI: 10.3122/jabfm.2018.01.170288.Peer-Reviewed Original ResearchConceptsUsual interstitial pneumonitisPulmonary fibrosisInterstitial pneumonitisCorrect diagnosisAccurate diagnosisUIP/IPFChronic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisNonspecific interstitial pneumonitisPulmonary fibrotic diseasesAmerican Thoracic SocietyAntifibrotic medicationsFibrotic sarcoidosisMean life expectancySerologic testingWorse prognosisCareful historyHypersensitivity pneumonitisThoracic SocietyFibrotic pathwaysInvasive proceduresClinician's abilityFibrotic diseasesPneumonitisFibrosis
2017
Elevated serum D-dimer level is associated with an increased risk of acute exacerbation in interstitial lung disease
Ishikawa G, Acquah SO, Salvatore M, Padilla ML. Elevated serum D-dimer level is associated with an increased risk of acute exacerbation in interstitial lung disease. Respiratory Medicine 2017, 128: 78-84. PMID: 28610674, DOI: 10.1016/j.rmed.2017.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlveolitis, Extrinsic AllergicBiomarkersChronic DiseaseDisease ProgressionFemaleFibrin Fibrinogen Degradation ProductsHospitalizationHumansIdiopathic Interstitial PneumoniasIdiopathic Pulmonary FibrosisL-Lactate DehydrogenaseLung Diseases, InterstitialMaleMiddle AgedMortalityOutcome Assessment, Health CarePredictive Value of TestsPrognosisPulmonary EmphysemaRetrospective StudiesRisk FactorsVenous ThromboembolismConceptsElevated serum D-dimer levelsSerum D-dimer levelsInterstitial lung diseaseD-dimer levelsAcute exacerbationRespiratory-related hospitalizationsSerum D-dimerD-dimer measurementVenous thromboembolismCause hospitalizationCause mortalityD-dimerLung diseaseOutcome measuresElevated serum D-dimerCollagen tissue diseasesSubsequent acute exacerbationChronic hypersensitivity pneumonitisSecondary outcome measuresHome oxygen therapyIdiopathic interstitial pneumoniaIdiopathic pulmonary fibrosisPrimary outcome measureSerum lactate dehydrogenaseInterstitial pneumonia