2023
The effects of elexafactor/tezafactor/ivacaftor beyond the epithelium: spurring macrophages to fight infections.
Bruscia E. The effects of elexafactor/tezafactor/ivacaftor beyond the epithelium: spurring macrophages to fight infections. European Respiratory Journal 2023, 61: 2300216. PMID: 37003613, DOI: 10.1183/13993003.00216-2023.Peer-Reviewed Original ResearchMeSH KeywordsAminophenolsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpitheliumHumansMacrophages
2022
Update on Innate and Adaptive Immunity in Cystic Fibrosis
Bruscia E, Bonfield T. Update on Innate and Adaptive Immunity in Cystic Fibrosis. Clinics In Chest Medicine 2022, 43: 603-615. PMID: 36344069, DOI: 10.1016/j.ccm.2022.06.004.Peer-Reviewed Original ResearchMeSH KeywordsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansImmunity, InnateInflammationLungPneumoniaConceptsChronic infectionCFTR modulator therapyRobust inflammatory responseCystic fibrosis pathophysiologyImmune dysregulationPatient ageExcessive inflammationModulator therapyLung microenvironmentLung infectionImmune mechanismsInflammatory responseAdaptive immunityMucociliary transportCF life expectancyCF lungCystic fibrosisInfectionLife expectancyImmunityCritical roleCurrent understandingMorbidityInflammationFibrosisRecruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansInflammationLungMacrophagesMiceMonocytesPneumoniaReceptors, ChemokineTransforming Growth Factor betaConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetEmerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis
Jaganathan D, Bruscia EM, Kopp BT. Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis. International Journal Of Molecular Sciences 2022, 23: 7750. PMID: 35887098, PMCID: PMC9319215, DOI: 10.3390/ijms23147750.Peer-Reviewed Original ResearchMeSH KeywordsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansInflammationMacrophagesPhagocytosisConceptsPhagosome formationCystic fibrosis transmembrane conductance regulator (CFTR) geneTransmembrane conductance regulator geneInnate immunityTissue homeostasisRegulator geneMutant CFTRCF macrophagesCystic fibrosisPhagocytic mechanismsPathogenic microbesAdaptive immune systemDefective macrophage phagocytosisCFTRCurrent understandingTherapeutic developmentCentral roleMacrophage phagocytosisCFTR modulatorsPhagocytic cellsPhagocytosisNew therapeutic developmentsMacrophages contributesLung functionChronic inflammation
2017
Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages
Di Pietro C, Zhang PX, O’Rourke T, Murray TS, Wang L, Britto CJ, Koff JL, Krause DS, Egan ME, Bruscia EM. Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages. Scientific Reports 2017, 7: 10882. PMID: 28883468, PMCID: PMC5589856, DOI: 10.1038/s41598-017-11012-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytoskeletal ProteinsDisease Models, AnimalMacrophage ActivationMacrophagesMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionToll-Like Receptor 4ConceptsCystic fibrosis transmembrane conductance regulatorPI3K/AktFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorPI3K/Akt signalingConductance regulatorAnti-bacterial immune responseAkt signalingAltered localizationEzrinCystic fibrosis diseaseMφ activationAktProtein levelsFibrosis diseaseActivationImmune regulationPhagocytosisInductionDirect linkSignalingRegulatorImmune responseMΦMacrophages
2016
Cystic Fibrosis Lung Immunity: The Role of the Macrophage
Bruscia EM, Bonfield TL. Cystic Fibrosis Lung Immunity: The Role of the Macrophage. Journal Of Innate Immunity 2016, 8: 550-563. PMID: 27336915, PMCID: PMC5089923, DOI: 10.1159/000446825.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpigenesis, GeneticHomeostasisHumansImmunity, InnateInfectionsInflammationLungMacrophages, AlveolarConceptsLung homeostasisCystic fibrosis pathophysiologyTranscriptional shiftMortality of patientsEnvironmental cuesAdaptive immune networkModifier genesMΦ functionMajor morbidityExcessive inflammationMΦ phenotypeLung infectionCF lungCFTR dysfunctionMajor playersHomeostasisDiseaseMacrophagesIntrinsic changesGenesImmune networkPhenotypeMorbidityInflammationPatientsIncreased susceptibility of Cftr−/− mice to LPS-induced lung remodeling
Bruscia E, Zhang P, Barone C, Scholte BJ, Homer R, Krause D, Egan ME. Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2016, 310: l711-l719. PMID: 26851259, PMCID: PMC4836110, DOI: 10.1152/ajplung.00284.2015.Peer-Reviewed Original ResearchMeSH KeywordsAirway RemodelingAnimalsChemokine CXCL10Cystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorLipopolysaccharidesLungMice, 129 StrainMice, Inbred C57BLMice, Inbred CFTRMice, KnockoutPneumoniaRespiratory MucosaConceptsLung pathologyCF miceImmune responseWT miceChronic inflammationCystic fibrosisAbnormal immune responseChronic pulmonary infectionPersistent immune responseWild-type littermatesCF mouse modelsPseudomonas aeruginosa lipopolysaccharideCF lung pathologyPulmonary infectionChronic administrationLPS exposurePersistent inflammationLung remodelingWT littermatesLung tissueOverall pathologyMouse modelInflammationChronic exposureBacterial products
2013
Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator
Villella VR, Esposito S, Bruscia EM, Vicinanza M, Cenci S, Guido S, Pettoello-Mantovani M, Carnuccio R, De Matteis MA, Luini A, Maiuri MC, Raia V, Kroemer G, Maiuri L. Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator. Cell Death & Differentiation 2013, 20: 1101-1115. PMID: 23686137, PMCID: PMC3705602, DOI: 10.1038/cdd.2013.46.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsBeclin-1BronchiCell LineCell MembraneCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsHumansMembrane ProteinsMutationPhosphoric Monoester HydrolasesProteostasis DeficienciesRab5 GTP-Binding ProteinsReceptors, TransferrinSequestosome-1 ProteinConceptsCFTR proteinBronchial epithelial cellsCFTR surface expressionSmall GTPase Rab5Cystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorWild-type CFTRFunctional CFTR proteinSQSTM1/p62Transmembrane conductance regulatorPositive feed-forward loopPlasma membrane stabilityFeed-forward loopEpithelial cellsProteostasis regulationProtein traffickingProteostasis networkGTPase Rab5Rab5 effectorProteostasis regulatorsConformational diseasesCystic fibrosis transmembrane conductance regulator (CFTR) potentiatorRecycling defectsSQSTM1 accumulationUnexpected linkReduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator
Zhang PX, Murray TS, Villella VR, Ferrari E, Esposito S, D'Souza A, Raia V, Maiuri L, Krause DS, Egan ME, Bruscia EM. Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator. The Journal Of Immunology 2013, 190: 5196-5206. PMID: 23606537, PMCID: PMC3711148, DOI: 10.4049/jimmunol.1201607.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCaveolin 1Cells, CulturedChildChild, PreschoolCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorFemaleHeme Oxygenase-1HumansInflammationLipopolysaccharidesLung DiseasesMacrophagesMaleMembrane ProteinsMiceMice, KnockoutNasal PolypsReactive Oxygen SpeciesSignal TransductionToll-Like Receptor 4Young AdultConceptsCav-1 expressionHeme oxygenase-1Dysfunctional cystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulatorCell surfaceFibrosis transmembrane conductance regulatorProtein caveolin-1Cellular redox statusCell surface localizationCellular oxidative stateTransmembrane conductance regulatorHO-1 enzymePositive feed-forward loopCystic fibrosis macrophagesNegative regulatorCaveolin-1Conductance regulatorCell survivalHO-1 deliverySurface localizationRedox statusMΦ responsesHO-1/CO pathwayPathwayPotential target
2008
Macrophages Directly Contribute to the Exaggerated Inflammatory Response in Cystic Fibrosis Transmembrane Conductance Regulator−/− Mice
Bruscia EM, Zhang PX, Ferreira E, Caputo C, Emerson JW, Tuck D, Krause DS, Egan ME. Macrophages Directly Contribute to the Exaggerated Inflammatory Response in Cystic Fibrosis Transmembrane Conductance Regulator−/− Mice. American Journal Of Respiratory Cell And Molecular Biology 2008, 40: 295-304. PMID: 18776130, PMCID: PMC2645527, DOI: 10.1165/rcmb.2008-0170oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationBronchoalveolar Lavage FluidCells, CulturedCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytokinesImmunity, InnateLipopolysaccharidesMacrophagesMiceMice, TransgenicPseudomonas InfectionsConceptsExaggerated inflammatory responseExaggerated immune responseBone marrow-derived macrophagesIL-6Marrow-derived macrophagesCystic fibrosisCF miceKeratinocyte chemoattractantCytokine responsesInflammatory responseIL-1alphaImmune responseAlveolar macrophagesBronchoalveolar lavage fluidGranulocyte colony-stimulating factorNumber of neutrophilsChemoattractant protein-1CF lung diseaseElevated cytokine responseInnate immune systemImportant therapeutic targetCF mouse modelsPopulation of macrophagesColony-stimulating factorPseudomonas aeruginosa LPSCftr gene targeting in mouse embryonic stem cells mediated by Small Fragment Homologous Replacement (SFHR).
Sangiuolo F, Scaldaferri ML, Filareto A, Spitalieri P, Guerra L, Favia M, Caroppo R, Mango R, Bruscia E, Gruenert DC, Casavola V, De Felici M, Novelli G. Cftr gene targeting in mouse embryonic stem cells mediated by Small Fragment Homologous Replacement (SFHR). Frontiers In Bioscience-Landmark 2008, 13: 2989-99. PMID: 17981772, PMCID: PMC3725395, DOI: 10.2741/2904.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCloning, MolecularCystic Fibrosis Transmembrane Conductance RegulatorDNAEmbryonic Stem CellsGene TargetingGenetic TechniquesMiceMicroscopy, FluorescenceMicroscopy, VideoMotor NeuronsMutationReverse Transcriptase Polymerase Chain ReactionRNAStem CellsConceptsSmall fragment homologous replacementES cellsSmall DNA fragmentsGene functionHomologous replacementEmbryonic stem cell genomeMouse embryonic stem cell genomeGenomic DNAMurine ES cellsTissue-specific gene functionEndogenous genomic DNAMouse embryonic stem cellsSpecific genomic lociStem cell genomeNormal gene functionCFTR-dependent chloride effluxEmbryonic stem cellsDifferent cell lineagesGene correctionGenomic lociGenomic sequencesCFTR locusCell genomeDifferent genesCell lineagesRectal Potential Difference and the Functional Expression of CFTR in the Gastrointestinal Epithelia in Cystic Fibrosis Mouse Models
Weiner SA, Caputo C, Bruscia E, Ferreira EC, Price JE, Krause DS, Egan ME. Rectal Potential Difference and the Functional Expression of CFTR in the Gastrointestinal Epithelia in Cystic Fibrosis Mouse Models. Pediatric Research 2008, 63: 73-78. PMID: 18043508, DOI: 10.1203/pdr.0b013e31815b4bc6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzoatesColforsinColonCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDisease Models, AnimalGenotypeIntestinal MucosaMembrane PotentialsMiceMice, Inbred CFTRMice, Mutant StrainsPhenotypeRectumReproducibility of ResultsThiazolidinesConceptsRectal potential differenceMouse modelCF mouse modelsCystic fibrosisFibrosis mouse modelDifferent mouse modelsCystic fibrosis mouse modelUssing chamber methodEffects of interventionsAutosomal recessive diseasePharmacologic interventionsRespiratory epitheliumElectrophysiologic phenotypeGastrointestinal epitheliumCF transmembrane conductance regulator (CFTR) geneRecessive diseaseVivo methodsVivo assaysVivo dataCFTR functionTransmembrane conductance regulator geneReliable assayEpitheliumInterventionCFTR expression
2006
Engraftment of Donor‐Derived Epithelial Cells in Multiple Organs Following Bone Marrow Transplantation into Newborn Mice
Bruscia EM, Ziegler EC, Price JE, Weiner S, Egan ME, Krause DS. Engraftment of Donor‐Derived Epithelial Cells in Multiple Organs Following Bone Marrow Transplantation into Newborn Mice. Stem Cells 2006, 24: 2299-2308. PMID: 16794262, DOI: 10.1634/stemcells.2006-0166.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBone Marrow TransplantationCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsFemaleFluorescent Antibody TechniqueHematopoietic Stem Cell TransplantationIn Situ Hybridization, FluorescenceMaleMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicRNA, MessengerY ChromosomeConceptsBone marrow-derived cellsMarrow-derived epithelial cellsBone marrow transplantationNewborn miceEpithelial cellsMarrow transplantationGI tractBone marrow-derived epithelial cellsDonor-derived epithelial cellsDoses of busulfanMarrow-derived cellsEngraftment of donorIrradiated adult recipientsMyeloablative regimenPreparative regimenAdult recipientsDifferent regimensEngrafted miceHematopoietic engraftmentGastrointestinal tractSurvival advantageTherapeutic benefitAdult miceMultiple organsBone marrowAssessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation
Bruscia EM, Price JE, Cheng EC, Weiner S, Caputo C, Ferreira EC, Egan ME, Krause DS. Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 2965-2970. PMID: 16481627, PMCID: PMC1413802, DOI: 10.1073/pnas.0510758103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorGastric MucosaGenetic TherapyIntestinal MucosaMiceMice, Inbred CFTRNasal MucosaRNA, MessengerConceptsCftr-/- miceEpithelial cellsNasal epitheliumBM-derived cellsBone marrow transplantationWild-type BMAirway epithelial cellsCystic fibrosis transmembrane conductance regulator (CFTR) activityCystic fibrosis miceRare epithelial cellsCftr-null miceMarrow transplantationBM transplantationFibrosis miceRespiratory tractCFTR activityGI tractBone marrowGastrointestinalChloride secretionCFTR-dependent chloride secretionIndividual miceTransplantationDifferent dosesMice
2002
Isolation of CF cell lines corrected at ΔF508-CFTR locus by SFHR-mediated targeting
Bruscia E, Sangiuolo F, Sinibaldi P, Goncz KK, Novelli G, Gruenert DC. Isolation of CF cell lines corrected at ΔF508-CFTR locus by SFHR-mediated targeting. Gene Therapy 2002, 9: 683-685. PMID: 12032687, DOI: 10.1038/sj.gt.3301741.Peer-Reviewed Original ResearchMeSH KeywordsCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGene TargetingGenetic TherapyHumansRespiratory SystemReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTransfectionConceptsSmall fragment homologous replacementAllele-specific PCRPrimer extension productsCell linesCFTR mRNAHuman airway epithelial cellsAllele-specific PCR amplificationΔF508 mutationCF transmembrane conductance regulator (CFTR) proteinExon 10CF cell lineMutant cell linesPCR amplificationAirway epithelial cellsEpithelial cellsGenomic DNA fingerprintingEndogenous CFTRHomologous replacementRegulator proteinDNA fingerprint analysisGenomic DNAWT mRNADNA fragmentsΔF508 alleleSequence analysisTowards the pharmacogenomics of cystic fibrosis
Sangiuolo F, DApice M, Bruscia E, Lucidi V, Novelli G. Towards the pharmacogenomics of cystic fibrosis. Pharmacogenomics 2002, 3: 75-87. PMID: 11966405, DOI: 10.1517/14622416.3.1.75.Peer-Reviewed Original ResearchMeSH KeywordsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorGenetic TherapyGenomicsGenotypeHumansMutationPhenotypeConceptsCystic fibrosisPancreatic insufficiencyChronic obstructive lung diseaseRelated clinical diseasesObstructive lung diseaseElevated sweat chloride concentrationsExocrine pancreatic insufficiencySweat chloride concentrationCongenital bilateral absenceMultiorgan diseaseChronic pancreatitisClinical symptomsLung diseaseDrug therapyClinical diseaseClinical overlapRecessive genetic diseaseTherapeutic questionsBilateral absenceDrug efficacyDiseaseVas deferensTherapy approachesFibrosisSymptoms