2024
Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAkt
2022
Recruited 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 ResearchConceptsC 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 targetRecruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis
Di Pietro C, Öz HH, Zhang PX, Cheng EC, Martis V, Bonfield TL, Kelley TJ, Jubin R, Abuchowski A, Krause DS, Egan ME, Murray TS, Bruscia EM. Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis. Experimental & Molecular Medicine 2022, 54: 639-652. PMID: 35581352, PMCID: PMC9166813, DOI: 10.1038/s12276-022-00770-8.Peer-Reviewed Original ResearchConceptsHeme oxygenase-1Cystic fibrosisOxygenase-1Myeloid differentiation factor 88Neutrophilic pulmonary inflammationChronic airway infectionDifferentiation factor 88HO-1 levelsDisease mouse modelPseudomonas aeruginosaRecruitment of monocytesResolution of inflammationMonocytes/macrophagesTreatment of CFConditional knockout miceMechanism of actionLung neutrophiliaNeutrophilic inflammationLung inflammationAirway infectionPulmonary diseasePulmonary inflammationFactor 88Lung damageProinflammatory cytokines
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
2013
Reduced 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
2011
Microbiota regulates immune defense against respiratory tract influenza A virus infection
Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 5354-5359. PMID: 21402903, PMCID: PMC3069176, DOI: 10.1073/pnas.1019378108.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionVirus infectionDendritic cellsImmune responseCommensal bacteriaRespiratory influenza virus infectionToll-like receptor ligandsVirus-specific CD4CD8 T cellsT cell primingCommensal microbiota compositionProductive immune responseExpression of mRNADistal injectionLymph nodesImmune impairmentIntact microbiotaIL-1βAntibody responseImmune homeostasisRespiratory mucosaAntibiotic treatmentT cellsInflammasome activationCommensal microbiota
2009
Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection
Lan L, Murray TS, Kazmierczak BI, He C. Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection. Molecular Microbiology 2009, 75: 76-91. PMID: 19943895, PMCID: PMC2881571, DOI: 10.1111/j.1365-2958.2009.06955.x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsAnti-Bacterial AgentsBeta-Lactam ResistanceBeta-LactamsFemaleGene DeletionGene Expression Regulation, BacterialGlutathione PeroxidaseHydrogen PeroxideMiceMice, Inbred C57BLModels, BiologicalMutagenesis, Site-DirectedOxidative StressPigments, BiologicalPneumoniaPseudomonas aeruginosaPseudomonas InfectionsQuorum SensingRepressor ProteinsSignal TransductionStress, PhysiologicalTyrosineVirulenceConceptsOxidative stress sensingCys-24Stress sensingPigment productionNull mutant strainOxidative stressSerine substitution mutantsGlobal regulatorPromoter DNASubstitution mutantsAdditional genesInside hostsQuorum sensingCys residuesMutant strainConstitutive expressionMultiple pathwaysRegulatory effectsBeta-lactam resistanceGenesSignificant inductionRegulatorTyrosine metabolismOSPRP. aeruginosa
2006
Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa
Kazmierczak BI, Lebron MB, Murray TS. Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa. Molecular Microbiology 2006, 60: 1026-1043. PMID: 16677312, PMCID: PMC3609419, DOI: 10.1111/j.1365-2958.2006.05156.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell MovementCyclic GMPEscherichia coli ProteinsFemaleFimbriae, BacterialHeLa CellsHumansMiceMice, Inbred C57BLPhosphoric Diester HydrolasesPhosphorus-Oxygen LyasesPneumonia, BacterialPoint MutationProtein Structure, TertiaryPseudomonas aeruginosaSequence DeletionVirulenceConceptsEAL domainBacterial poleGGDEF-EAL proteinsCyclic dimeric guanosine monophosphateDiguanylate cyclase activityPolar surface structuresType IV piliWild-type strainGGDEF domainDiguanylate cyclasesREC domainLocalization signalPilus assemblyGGDEFNon-polar sitesFimXSurface piliPseudomonas aeruginosaPhosphodiesterase activityBiofilm formationProteinMutantsPiliMotilityDomain