2024
Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Feng J, Kim J, Wang V, Chang D, Liu H, Bain W, Robinson K, Jie Z, Kotenko S, Dela Cruz C, Sharma L. Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries. Physiological Reports 2024, 12: e70104. PMID: 39455422, PMCID: PMC11511623, DOI: 10.14814/phy2.70104.Peer-Reviewed Original ResearchConceptsIII interferon signalingType III interferon signalingLung injuryInterferon signalingBleomycin-induced weight lossInflammatory responseModel of lung injuryBacterial pathogen Pseudomonas aeruginosaAcute lung injuryPathogen Pseudomonas aeruginosaBacterial endotoxin LPSChemotherapeutic agent bleomycinType III interferonsAnti-inflammatory roleIncreased inflammatory signalingLate time pointsBleomycin modelKnockout miceEndotoxin LPSIII interferonsAntiviral cytokinesDay 3Inflammatory signalingEarly injuryImpaired recoveryIntranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virus
2023
VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetmicroRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouse
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 efficacyCoronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction.
Peng X, Kim J, Gupta G, Agaronyan K, Mankowski MC, Korde A, Takyar SS, Shin HJ, Habet V, Voth S, Audia JP, Chang D, Liu X, Wang L, Cai Y, Tian X, Ishibe S, Kang MJ, Compton S, Wilen CB, Dela Cruz CS, Sharma L. Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction. The Journal Of Immunology 2022, 209: 1314-1322. PMID: 36165196, PMCID: PMC9523490, DOI: 10.4049/jimmunol.2200198.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Bacterial infectionsMouse modelCoronavirus infectionLysosomal dysfunctionMajor health care challengeLung immune cellsLung tissue damageSecondary bacterial infectionImpair host immunityIL-1β releaseHealth care challengesCell deathPyroptotic cell deathBacterial killing abilityIL-1βBacterial clearanceImmune cellsSecondary infectionHost immunityAlveolar macrophagesTissue damageΒ-coronavirusStructural cellsCare challengesEpidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury
Harris ZM, Sun Y, Joerns J, Clark B, Hu B, Korde A, Sharma L, Shin HJ, Manning EP, Placek L, Unutmaz D, Stanley G, Chun H, Sauler M, Rajagopalan G, Zhang X, Kang MJ, Koff JL. Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia‐Induced Lung Injury. Oxidative Medicine And Cellular Longevity 2022, 2022: 9518592. PMID: 36193076, PMCID: PMC9526641, DOI: 10.1155/2022/9518592.Peer-Reviewed Original ResearchConceptsAcute lung injuryEpidermal growth factor receptorAlveolar epithelial cellsLung injurySevere hyperoxiaEGFR inhibitionEpithelial cellsHyperoxia-Induced Lung InjuryRole of EGFRMurine alveolar epithelial cellsGrowth factor receptor inhibitionWorse clinical outcomesEpidermal growth factor receptor inhibitionHuman alveolar epithelial cellsWild-type littermatesPoly (ADP-ribose) polymeraseTerminal dUTP nickGrowth factor receptorClinical outcomesImproved survivalReceptor inhibitionLung repairProtective roleComplex roleEGFR deletion
2021
PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology.
Kim SH, Shin HJ, Yoon CM, Lee SW, Sharma L, Dela Cruz CS, Kang MJ. PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology. American Journal Of Respiratory Cell And Molecular Biology 2021, 64: 592-603. PMID: 33577398, PMCID: PMC8086043, DOI: 10.1165/rcmb.2020-0490oc.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBleomycinEpithelial CellsGene Expression RegulationHEK293 CellsHumansImmunity, InnateInflammasomesInfluenza A virusLungMiceMice, KnockoutMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinOrthomyxoviridae InfectionsPeroxisomesProtein AggregatesProtein BindingProtein KinasesPulmonary FibrosisSignal TransductionConceptsMAVS aggregationPINK1 deficiencyBimolecular fluorescence complementation analysisAntiviral innate immuneAppropriate cellular functionsKey molecular processesIntracellular signaling pathwaysInnate immune signalingComplementation analysisCellular functionsIntracellular perturbationsImmune signalingSignaling pathwaysPINK1Molecular processesMitochondria dysfunctionMAVSMAVS signalingMurine modelingSignalingFunctional significanceInnate immuneImportant roleRegulationNew roleRIPK3 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
Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia
Gautam S, Cohen AJ, Stahl Y, Toro P, Young GM, Datta R, Yan X, Ristic NT, Bermejo SD, Sharma L, Restrepo M, Dela Cruz CS. Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia. Thorax 2020, 75: 974-981. PMID: 32826284, DOI: 10.1136/thoraxjnl-2020-214896.Peer-Reviewed Original ResearchConceptsPure viral infectionBacterial coinfectionViral infectionInfluenza infectionSevere respiratory viral infectionsAbility of procalcitoninRetrospective cohort studyViral respiratory infectionsRespiratory viral infectionsMarker of severityRespiratory viral illnessSevere viral infectionsSpecificity of procalcitoninCharacteristic curve analysisCellular modelHigher procalcitoninProcalcitonin expressionElevated procalcitoninCohort studyViral illnessRespiratory infectionsAntibiotic administrationBacterial pneumoniaSevere diseaseProcalcitoninQuantification 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 diseasesDifferential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages
Chang D, Feng J, Liu H, Liu W, Sharma L, Dela Cruz CS. Differential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages. Innate Immunity 2020, 26: 618-626. PMID: 32762278, PMCID: PMC7556185, DOI: 10.1177/1753425920942582.Peer-Reviewed Original ResearchConceptsAkt pathwayEpithelial cellsCell typesKey cellular pathwaysLung epitheliumActivation of AktPhagocytic abilityMultiple cell typesAkt inhibitor MK2206Particular bacterial infectionsCellular pathwaysLung epithelial cellsMacrophage cell lineHost cellsBacterial infectionsRespiratory epithelial cellsCell proliferationType of infectionCell linesPathwayHost defenseDifferential rolesAktSC-79CellsHarnessing Murine Microbiome Models to Study Human Lung Microbiome
Chang D, Sharma L, Dela Cruz CS. Harnessing Murine Microbiome Models to Study Human Lung Microbiome. CHEST Journal 2020, 157: 776-778. PMID: 32252931, PMCID: PMC7926993, DOI: 10.1016/j.chest.2019.12.011.Commentaries, Editorials and Letters
2019
Measurement of Chitinase Activity in Biological Samples.
Amick AK, Liu Q, Gautam S, Chupp G, Dela Cruz CS, Sharma L. Measurement of Chitinase Activity in Biological Samples. Journal Of Visualized Experiments 2019 PMID: 31498326, DOI: 10.3791/60159.Peer-Reviewed Original ResearchConceptsDisease severityType 2 inflammatory diseasesPulmonary fibrosisAllergic diseasesInflammatory diseasesHost immunityReliable biomarkersTherapeutic effectivenessGaucher diseaseHost defenseSerum samplesDiseaseChitinase-like proteinsGenetic disordersHuman subjectsPrecise roleImportant biomarkerBiomarkersSeverityImportant roleChitinase levelsAsthmaPatientsFibrosisMiceToll-Like Receptors 2 and 4 Modulate Pulmonary Inflammation and Host Factors Mediated by Outer Membrane Vesicles Derived from Acinetobacter baumannii
Marion CR, Lee J, Sharma L, Park KS, Lee C, Liu W, Liu P, Feng J, Gho YS, Dela Cruz CS. Toll-Like Receptors 2 and 4 Modulate Pulmonary Inflammation and Host Factors Mediated by Outer Membrane Vesicles Derived from Acinetobacter baumannii. Infection And Immunity 2019, 87: 10.1128/iai.00243-19. PMID: 31262980, PMCID: PMC6704609, DOI: 10.1128/iai.00243-19.Peer-Reviewed Original ResearchConceptsToll-like receptorsPulmonary inflammationOuter membrane vesiclesToll-like receptor 2TLR4-deficient miceVentilator-associated pneumoniaWild-type miceSystemic inflammationNeutrophil recruitmentIntranasal introductionProinflammatory responseReceptor 2Acinetobacter baumanniiInflammationMouse lungHigh mortalityHost factorsWeight lossMicePneumoniaGram-negative bacteriumMembrane vesiclesGram-negative bacteriaTLR2ChemokinesMechanosensation of cyclical force by PIEZO1 is essential for innate immunity
Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG, Mack M, Schwartz MA, Dela Cruz CS, Palm NW, Jackson R, Flavell RA. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 2019, 573: 69-74. PMID: 31435009, PMCID: PMC6939392, DOI: 10.1038/s41586-019-1485-8.Peer-Reviewed Original ResearchConceptsInnate immune cellsImmune cellsInflammatory responseInnate immune systemCyclical hydrostatic pressurePulmonary inflammationImmune responseImmune systemInnate immunityBacterial infectionsIon channel Piezo1InflammationPhysiological fluctuationsImmunityPhysiological roleLocal microenvironmentCellsPiezo1Direct recognitionResponseAutoinflammationLungInfectionMiceA potential role of microvesicle-containing miR-223/142 in lung inflammation
Zhang D, Lee H, Wang X, Groot M, Sharma L, Dela Cruz CS, Jin Y. A potential role of microvesicle-containing miR-223/142 in lung inflammation. Thorax 2019, 74: 865-874. PMID: 31331947, PMCID: PMC7036165, DOI: 10.1136/thoraxjnl-2018-212994.Peer-Reviewed Original ResearchConceptsAcute lung injuryNLRP3 inflammasome activationLung inflammationInflammasome activationMacrophage-mediated inflammatory responsesBronchoalveolar lavage fluid samplesIntratracheal lipopolysaccharide (LPS) instillationUncontrolled lung inflammationInhibition of NLRP3Inflammatory lung responseLavage fluid samplesFunctions of microvesiclesLung injuryLipopolysaccharide instillationLung responseIntratracheal instillationInflammatory responseLung macrophagesMurine lungMacrophage activationMiR-223BALFInflammationLPSMiR-142
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 recoveryRegulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae
Sharma L, Amick AK, Vasudevan S, Lee SW, Marion CR, Liu W, Brady V, Losier A, Bermejo SD, Britto CJ, Lee CG, Elias JA, Dela Cruz CS. Regulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae. The Journal Of Immunology 2018, 201: 615-626. PMID: 29891554, PMCID: PMC6291403, DOI: 10.4049/jimmunol.1701782.Peer-Reviewed Original ResearchConceptsLung infectionMouse modelRole of chitotriosidaseBronchoalveolar lavage fluidNumber of neutrophilsSimilar inflammatory responseRole of CHIT1Antibiotic therapyImproved survivalInflammatory changesLavage fluidInflammatory responseNeutrophil proteasesBacterial disseminationTrue chitinasesInfectionBeneficial effectsDetrimental roleAkt pathwayKlebsiella pneumoniaeAkt inhibitorCHIT1Chitinase-like proteinsMiceAkt activation
2014
Assessment of Phagocytic Activity of Cultured Macrophages Using Fluorescence Microscopy and Flow Cytometry
Sharma L, Wu W, Dholakiya SL, Gorasiya S, Wu J, Sitapara R, Patel V, Wang M, Zur M, Reddy S, Siegelaub N, Bamba K, Barile FA, Mantell LL. Assessment of Phagocytic Activity of Cultured Macrophages Using Fluorescence Microscopy and Flow Cytometry. Methods In Molecular Biology 2014, 1172: 137-145. PMID: 24908301, DOI: 10.1007/978-1-4939-0928-5_12.ChaptersMeSH KeywordsAnimalsCell LineFlow CytometryFluorescein-5-isothiocyanateFluorescent DyesGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorHMGB1 ProteinInterleukin-1betaMacrophagesMiceMicroscopy, FluorescenceMicrospheresPhagocytosisTransforming Growth Factor beta1Tumor Necrosis Factor-alphaConceptsCultured macrophagesHigh mobility group box 1Individual cellsInnate immune systemFluorescence microscopyNumerous diseasesPhagocytic processFluorescence microscopePhagocytic functionPhagocytic activityCell debrisPhagocytosisFlow cytometryMobility group box 1PhagocytesGroup box 1GM-CSFMacrophagesImmune systemTGF-β1Different cytokinesFlow cytometerIL-1βEngulfmentHomeostasis