2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacy
2021
RIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling during Streptococcus Infection.
Huang HR, Cho SJ, Harris RM, Yang J, Bermejo S, Sharma L, Dela Cruz CS, Xu JF, Stout-Delgado HW. RIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling during Streptococcus Infection. American Journal Of Respiratory Cell And Molecular Biology 2021, 64: 579-591. PMID: 33625952, PMCID: PMC8086037, DOI: 10.1165/rcmb.2020-0312oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsCalcium ChannelsCase-Control StudiesDisease Models, AnimalFemaleGene Expression RegulationHumansInflammasomesMacrophages, AlveolarMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMitochondriaMitochondrial Permeability Transition PoreNecroptosisNLR Family, Pyrin Domain-Containing 3 ProteinPneumonia, PneumococcalProtein KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesReceptor-Interacting Protein Serine-Threonine KinasesSignal TransductionStreptococcus pneumoniaeConceptsCommunity-acquired pneumoniaPneumococcal pneumoniaSevere pathological damageHealthy control subjectsPotential plasma markerNLRP3 inflammasome activationCommon bacterial pathogensMitochondrial permeability transition pore openingStreptococcal pneumoniaPlasma markersStreptococcus infectionBacterial clearanceControl subjectsPathological damageLeading causeMitochondrial reactive oxygenInflammasome activationMurine modelMitochondrial calcium uptakePneumoniaPermeability transition pore openingHuman studiesHigh mortalityInflammasome signalingTransition pore opening
2020
Quantification of bronchoalveolar neutrophil extracellular traps and phagocytosis in murine pneumonia
Gautam S, Stahl Y, Young GM, Howell R, Cohen AJ, Tsang DA, Martin T, Sharma L, Dela Cruz CS. Quantification of bronchoalveolar neutrophil extracellular traps and phagocytosis in murine pneumonia. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2020, 319: l661-l669. PMID: 32783617, PMCID: PMC7642899, DOI: 10.1152/ajplung.00316.2020.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trapsAcute respiratory distress syndromeChronic obstructive pulmonary diseaseNeutrophil responseExtracellular trapsDysregulation of neutrophilsObstructive pulmonary diseaseRespiratory distress syndromeNeutrophil effector functionsEx vivo assaysBronchoalveolar neutrophilsSevere asthmaDistress syndromeLung neutrophilsPulmonary diseaseMurine pneumoniaMurine modelEffector functionsNeutrophil researchMouse lungCystic fibrosisMethodologic issuesMurine researchLungArray of diseases
2018
Impact of Cigarette Smoke Exposure on the Lung Fibroblastic Response after Influenza Pneumonia
Lee SW, Sharma L, Kang YA, Kim SH, Chandrasekharan S, Losier A, Brady V, Bermejo S, Andrews N, Yoon CM, Liu W, Lee JY, Kang MJ, Dela Cruz CS. Impact of Cigarette Smoke Exposure on the Lung Fibroblastic Response after Influenza Pneumonia. American Journal Of Respiratory Cell And Molecular Biology 2018, 59: 770-781. PMID: 30110182, PMCID: PMC6293077, DOI: 10.1165/rcmb.2018-0004oc.Peer-Reviewed Original ResearchConceptsCigarette smoke exposureLungs of miceInfluenza infectionInfluenza virusBAL fluidSmoke exposureGrowth factor-β1 levelsAir-exposed lungsInfluenza-infected miceSignificant lung injuryFibroblastic responseLung-derived fibroblastsProtein-positive cellsGrowth factor-β1Influenza pneumoniaDifferent time pointsLung injurySmoking groupSignificant morbidityCS exposureMurine modelFibrotic responseΒ1 levelsFactor-β1Weight recovery