2022
ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor‐induced leak
Khan A, Ni W, Baltazar T, Lopez‐Giraldez F, Pober JS, Pierce RW. ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor‐induced leak. The FASEB Journal 2022, 36: e22254. PMID: 35294066, PMCID: PMC9103844, DOI: 10.1096/fj.202101873rr.Peer-Reviewed Original Research
2021
Tumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption
Khan A, Ni W, Lopez‐Giraldez F, Kluger MS, Pober JS, Pierce RW. Tumor necrosis factor‐induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption. The FASEB Journal 2021, 35: e21627. PMID: 33948992, PMCID: PMC9026622, DOI: 10.1096/fj.202002783rr.Peer-Reviewed Original ResearchConceptsCapillary endothelial cellsHuman dermal microvascular endothelial cellsMicrovascular endothelial cellsEndothelial cellsTight junctionsCultured human microvascular endothelial cellsEC tight junctionsLoss of barrierCapillary leak syndromeCapillary barrier functionDermal microvascular endothelial cellsRhoB activationTight junction disruptionDisrupts tight junctionsHuman microvascular endothelial cellsExtent of TNFHuman capillary endothelial cellsLeak syndromeOverwhelming inflammationCapillary leakBarrier lossTJ disruptionJunction disruptionRhoB knockdownTNF
2015
Tumor Necrosis Factor Disrupts Claudin-5 Endothelial Tight Junction Barriers in Two Distinct NF-κB-Dependent Phases
Clark PR, Kim RK, Pober JS, Kluger MS. Tumor Necrosis Factor Disrupts Claudin-5 Endothelial Tight Junction Barriers in Two Distinct NF-κB-Dependent Phases. PLOS ONE 2015, 10: e0120075. PMID: 25816133, PMCID: PMC4376850, DOI: 10.1371/journal.pone.0120075.Peer-Reviewed Original ResearchCell Membrane PermeabilityCells, CulturedClaudin-5DermisEndothelium, VascularHuman Umbilical Vein Endothelial CellsHumansMicroscopy, FluorescenceMyosin Light ChainsMyosin-Light-Chain KinaseNF-kappa BPhosphorylationRho-Associated KinasesRNA, Small InterferingSignal TransductionTight JunctionsTumor Necrosis Factor-alpha
2014
Rapamycin antagonizes TNF induction of VCAM-1 on endothelial cells by inhibiting mTORC2
Wang C, Qin L, Manes TD, Kirkiles-Smith NC, Tellides G, Pober JS. Rapamycin antagonizes TNF induction of VCAM-1 on endothelial cells by inhibiting mTORC2. Journal Of Experimental Medicine 2014, 211: 395-404. PMID: 24516119, PMCID: PMC3949571, DOI: 10.1084/jem.20131125.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceBlotting, WesternCell AdhesionChromatin ImmunoprecipitationDNA PrimersEndothelial CellsFlow CytometryHumansImmunoblottingMechanistic Target of Rapamycin Complex 2Microscopy, FluorescenceMultiprotein ComplexesOncogene Protein v-aktReal-Time Polymerase Chain ReactionSirolimusT-LymphocytesTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1ConceptsVascular cell adhesion molecule-1VCAM-1 expressionEndothelial cellsActivation of ERK1/2Cell adhesion molecule-1TNF inductionInfiltration of leukocytesAdhesion molecule-1Inhibition of TNFPotential therapeutic targetAbility of rapamycinAbility of TNFTranscription factor IRF-1Hyperactivation of ERK1/2Inhibition of ERK1/2Venular flowT cellsEndothelial expressionInflamed tissuesVascular endotheliumMolecule-1Therapeutic targetRapamycin pretreatmentRenal glomeruliTNF
2009
TNF Receptors Differentially Signal and Are Differentially Expressed and Regulated in the Human Heart
Al-Lamki R, Brookes AP, Wang J, Reid MJ, Parameshwar J, Goddard MJ, Tellides G, Wan T, Min W, Pober JS, Bradley JR. TNF Receptors Differentially Signal and Are Differentially Expressed and Regulated in the Human Heart. American Journal Of Transplantation 2009, 9: 2679-2696. PMID: 19788501, PMCID: PMC3517885, DOI: 10.1111/j.1600-6143.2009.02831.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell CycleCell DeathEndothelium, VascularEnzyme ActivationGraft RejectionHeart TransplantationHumansMAP Kinase Kinase Kinase 5MiceMice, KnockoutMyocardiumMyocytes, CardiacOrgan Culture TechniquesProtein-Tyrosine KinasesReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIRNA, MessengerTumor Necrosis Factor-alphaConceptsVascular endothelial cellsCardiac allograftsCell cycle entryApoptosis signal-regulating kinase 1Cycle entryExpression of TNFTNFR1 knockoutNecrosis factorTarget cell responseTNFTNF receptorCardiac fibroblastsCell responsesSignal-regulated kinases 1TNF responseASK1 activationMyocardiumEndothelial cellsEpithelial tyrosine kinaseTNFR2Human heartOrgan cultureTNFR1Etk activationAllografts
2006
Endothelial Cell Dysfunction, Injury and Death
Pober JS, Min W. Endothelial Cell Dysfunction, Injury and Death. Handbook Of Experimental Pharmacology 2006, 176/II: 135-156. PMID: 16999227, DOI: 10.1007/3-540-36028-x_5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisEndothelium, VascularGranzymesHumansInflammationMacrophagesNeutrophilsReactive Oxygen SpeciesSignal TransductionT-Lymphocytes, CytotoxicTumor Necrosis Factor-alphaConceptsTumor necrosis factorCytolytic T lymphocytesEC injuryEndothelial cellsReactive oxygen speciesEndothelial cell dysfunctionMacrophage-derived cytokinesVascular endothelial cellsEndothelial dysfunctionNecrosis factorCell dysfunctionT lymphocytesInjuryCommon mediatorInflammationDysfunctionDeathOxygen speciesCytokinesLymphocytesNeutrophilsDifferent agentsBiochemical pathways
2001
Expression of Tumor Necrosis Factor Receptors in Normal Kidney and Rejecting Renal Transplants
Al-Lamki R, Wang J, Skepper J, Thiru S, Pober J, Bradley J. Expression of Tumor Necrosis Factor Receptors in Normal Kidney and Rejecting Renal Transplants. Laboratory Investigation 2001, 81: 1503-1515. PMID: 11706058, DOI: 10.1038/labinvest.3780364.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAntigens, CDColoring AgentsEosine Yellowish-(YS)Fluorescent DyesGene ExpressionGraft RejectionHematoxylinHumansKidneyKidney Failure, ChronicKidney TransplantationMicroscopy, ImmunoelectronReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaConceptsDistal convoluted tubuleNormal kidneyTubular epithelial cellsTNFR-1Renal transplantEpithelial cellsTNFR-2Acute cellular rejectionTNFR-1 expressionAcute transplant rejectionTumor necrosis factor receptorEndothelium of glomeruliNecrosis factor receptorInteraction of TNFAcute rejectionCellular rejectionTNFR expressionTransplant rejectionCultured cellsConvoluted tubulesRenal kidneyTNF receptorTNFKidneyHuman kidneyTNF Signaling in Vascular Endothelial Cells
Madge L, Pober J. TNF Signaling in Vascular Endothelial Cells. Experimental And Molecular Pathology 2001, 70: 317-325. PMID: 11418010, DOI: 10.1006/exmp.2001.2368.Peer-Reviewed Original ResearchConceptsTumor necrosis factorEndothelial cellsProinflammatory cytokine tumor necrosis factorCytokines tumor necrosis factorCultured human endothelial cellsVascular endothelial cellsHuman endothelial cellsNecrosis factorVascular endotheliumIntracellular pathwaysMajor targetTNF signalingCell typesCellsHUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1
Tereb D, Kirkiles-Smith N, Kim R, Wang Y, Rudic R, Schechner J, Lorber M, Bothwell A, Pober J, Tellides G. HUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1. Transplantation 2001, 71: 1622-1630. PMID: 11435975, DOI: 10.1097/00007890-200106150-00023.Peer-Reviewed Original ResearchConceptsTumor necrosis factorHuman tumor necrosis factorArtery graftT cellsNecrosis factorPig coronary artery endothelial cellsHuman T-cell infiltrationVascular cell adhesion molecule-1Human peripheral blood mononuclearHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsHuman leukocytesEndothelial cellsMajor histocompatibility complex antigensCell adhesion molecule-1Graft endothelial cellsT-cell infiltratesBeige mouse modelCoronary artery endothelial cellsT cell infiltrationCoronary artery graftsBlood mononuclear cellsPeripheral blood mononuclearCoronary artery segmentsAdhesion molecule-1Tumor Necrosis Factor Alpha Increases Human Cerebral Endothelial Cell Gb3 and Sensitivity to Shiga Toxin
Eisenhauer P, Chaturvedi P, Fine R, Ritchie A, Pober J, Cleary T, Newburg D. Tumor Necrosis Factor Alpha Increases Human Cerebral Endothelial Cell Gb3 and Sensitivity to Shiga Toxin. Infection And Immunity 2001, 69: 1889-1894. PMID: 11179369, PMCID: PMC98098, DOI: 10.1128/iai.69.3.1889-1894.2001.Peer-Reviewed Original ResearchMeSH KeywordsBlood-Brain BarrierDose-Response Relationship, DrugDrug SynergismEndothelium, VascularHumansShiga ToxinTrihexosylceramidesTumor Necrosis Factor-alphaConceptsHemolytic uremic syndromeShiga toxinMicrovascular brain endothelial cellsCentral nervous system pathologyTumor necrosis factor alphaEndothelial cellsShiga toxin toxicityNervous system pathologyBrain endothelial cellsNecrosis factor alphaTNF-alpha treatmentUmbilical vein endothelial cellsCNS involvementVein endothelial cellsUremic syndromeIntestinal infectionsShiga Toxin BindingFactor alphaEnterohemorrhagic Escherichia coliSystem pathologyFunctional receptorsNormal fatty acidsToxin bindingFatty acidsToxinEndothelial cell activation by tumor necrosis factor elicits human antiporcine cell-mediated rejection responses
Kirkiles-Smith NC, Tereb DA, Kim RW, McNiff JM, Schechner JS, Lorber MI, Pober JS, Tellides G. Endothelial cell activation by tumor necrosis factor elicits human antiporcine cell-mediated rejection responses. Transplantation Proceedings 2001, 33: 412-413. PMID: 11266888, DOI: 10.1016/s0041-1345(00)02072-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCytokinesEndothelium, VascularGraft RejectionHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansLymphocyte ActivationMiceMice, SCIDModels, AnimalSkin TransplantationSpecies SpecificitySwineT-LymphocytesTransplantation ChimeraTransplantation ToleranceTransplantation, HeterologousTumor Necrosis Factor-alpha
2000
The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization
Gaeta M, Johnson D, Kluger M, Pober J. The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization. Laboratory Investigation 2000, 80: 1185-1194. PMID: 10950109, DOI: 10.1038/labinvest.3780126.Peer-Reviewed Original ResearchConceptsDeath domainGolgi retentionPlasma membraneC-terminal death domainGolgi apparatusNF-kappaBDominant negative inhibitorWild-type receptorDisparate localizationTNF responseIntracellular domainC-terminusEndothelial cellsNegative inhibitorTNF signalsWild typeTumor necrosis factor receptor 1Chimeric receptorsFactor receptor 1Necrosis factor receptor 1Endogenous receptorsBasal expressionReceptor moleculesType receptorTNF actionHuman TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts
Kirkiles-Smith N, Tereb D, Kim R, McNiff J, Schechner J, Lorber M, Pober J, Tellides G. Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts. The Journal Of Immunology 2000, 164: 6601-6609. PMID: 10843720, DOI: 10.4049/jimmunol.164.12.6601.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAdultAnimalsCell Adhesion MoleculesDose-Response Relationship, ImmunologicDrug SynergismEndothelium, VascularGraft RejectionHistocompatibility AntigensHumansInterferon-gammaMiceMice, Inbred C57BLMice, SCIDMicrocirculationSevere Combined ImmunodeficiencySkin TransplantationSwineT-LymphocytesTransplantation, HeterologousTumor Necrosis Factor-alphaUp-RegulationConceptsHuman T-cell infiltrationPig skin xenograftsT cell infiltrationSkin xenograftsCell infiltrationHuman TNFIFN-gammaE-selectinT cell-mediated rejectionEndothelial cellsAdhesion moleculesCytokine-mediated injuryNonspecific inflammatory damagePig skin graftsCell-mediated rejectionAppropriate therapeutic targetsImmunodeficient mouse modelPorcine E-selectinEndothelial adhesion moleculesPorcine IFN-gammaClass II moleculesHuman skin allograftsMHC class IPorcine endothelial cellsImmunodeficient mouse hostsA Phosphatidylinositol 3-Kinase/Akt Pathway, Activated by Tumor Necrosis Factor or Interleukin-1, Inhibits Apoptosis but Does Not Activate NFκB in Human Endothelial Cells*
Madge L, Pober J. A Phosphatidylinositol 3-Kinase/Akt Pathway, Activated by Tumor Necrosis Factor or Interleukin-1, Inhibits Apoptosis but Does Not Activate NFκB in Human Endothelial Cells*. Journal Of Biological Chemistry 2000, 275: 15458-15465. PMID: 10748004, DOI: 10.1074/jbc.m001237200.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesApoptosisCells, CulturedChromonesCulture Media, Serum-FreeEndothelium, VascularEnzyme ActivationEnzyme InhibitorsHumansInterleukin-1KineticsMorpholinesNF-kappa BPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRecombinant ProteinsTumor Necrosis Factor-alphaUmbilical VeinsWortmanninConceptsHuman endothelial cellsProtein kinaseStress-activated protein kinaseAkt pathwayMitogen-activated protein kinaseProtein kinase AktPromoter-reporter geneInhibitor of phosphatidylinositolEndothelial cellsSerum-deprived endothelial cellsPhosphorylation of AktGrowth factorAnti-apoptotic pathwaysKinase AktGene productsAnti-apoptotic effectsInhibits ApoptosisSerum deprivationAktLY294002Phospho-AktPro-inflammatory gene productsTranscriptionKinasePhosphatidylinositolLarge-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors
Gatti E, Velleca M, Biedermann B, Ma W, Unternaehrer J, Ebersold M, Medzhitov R, Pober J, Mellman I. Large-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors. The Journal Of Immunology 2000, 164: 3600-3607. PMID: 10725716, DOI: 10.4049/jimmunol.164.7.3600.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, CD1Antigens, CD34Antigens, Differentiation, T-LymphocyteAntigens, NeoplasmCD40 LigandCell CountCell Culture TechniquesCell DifferentiationDendritic CellsGranulocyte Colony-Stimulating FactorHematopoietic Stem Cell TransplantationHumansImmunophenotypingLangerhans CellsLeukapheresisLigandsLipopolysaccharidesMembrane GlycoproteinsStem CellsTumor Necrosis Factor-alphaConceptsDendritic cellsLangerhans cellsT cell stimulationG-CSF-mobilized patientsManipulation of DCsImmature dendritic cellsIL-12 productionPrimary immune responseHuman Langerhans cellsCell stimulationDifferent proinflammatory stimuliToll family receptorsDC preparationsMaturation stimuliTNF-alphaCD40 ligandMHC productsImmune responseBirbeck granulesProinflammatory stimuliCytokine removalFamily receptorsAg processingDC typesHomogenous population
1999
Recent advances in the molecular basis of TNF signal transduction.
Ledgerwood EC, Pober JS, Bradley JR. Recent advances in the molecular basis of TNF signal transduction. Laboratory Investigation 1999, 79: 1041-50. PMID: 10496522.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell DeathGene Expression RegulationHumansInflammationReceptors, Tumor Necrosis FactorSignal TransductionSphingomyelin PhosphodiesteraseTumor Necrosis Factor-alphaApoptosis-inducing Agents Cause Rapid Shedding of Tumor Necrosis Factor Receptor 1 (TNFR1) A NONPHARMACOLOGICAL EXPLANATION FOR INHIBITION OF TNF-MEDIATED ACTIVATION*
Madge L, Sierra-Honigmann M, Pober J. Apoptosis-inducing Agents Cause Rapid Shedding of Tumor Necrosis Factor Receptor 1 (TNFR1) A NONPHARMACOLOGICAL EXPLANATION FOR INHIBITION OF TNF-MEDIATED ACTIVATION*. Journal Of Biological Chemistry 1999, 274: 13643-13649. PMID: 10224136, DOI: 10.1074/jbc.274.19.13643.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCalcium-Calmodulin-Dependent Protein KinasesCaspasesCells, CulturedDNA-Binding ProteinsEndothelium, VascularEnzyme ActivationEnzyme InhibitorsHumansI-kappa B ProteinsInterleukin-1Mitogen-Activated Protein KinasesNF-KappaB Inhibitor alphaP38 Mitogen-Activated Protein KinasesProteinsReceptors, Tumor Necrosis FactorSignal TransductionTNF Receptor-Associated Factor 1Tumor Necrosis Factor-alphaConceptsTumor necrosis factor receptor 1Apoptogenic drugsIkappaBalpha degradationTNF-dependent recruitmentBroad spectrum caspase inhibitor zVADfmkInitiation of apoptosisCaspase inhibitor zVADfmkApoptotic cell deathApoptosis-inducing agentsEndothelial cellsTumour necrosis factor signalFactor signalsP38 kinaseTNF signalingEvidence of apoptosisCell deathFactor receptor 1Necrosis factor receptor 1Inhibition of TNFArachidonyl trifluoromethylketoneVascular endothelial cellsApoptosisTRADDEC apoptosisPutative inhibitorsTNF recruits TRADD to the plasma membrane but not the trans-Golgi network, the principal subcellular location of TNF-R1.
Jones S, Ledgerwood E, Prins J, Galbraith J, Johnson D, Pober J, Bradley J. TNF recruits TRADD to the plasma membrane but not the trans-Golgi network, the principal subcellular location of TNF-R1. The Journal Of Immunology 1999, 162: 1042-8. PMID: 9916731, DOI: 10.4049/jimmunol.162.2.1042.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAortaBrefeldin ACattleCell CompartmentationCell Line, TransformedCell MembraneEndothelium, VascularGolgi ApparatusHumansMicroscopy, ConfocalProteinsReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type ISubcellular FractionsTNF Receptor-Associated Factor 1TransfectionTumor Necrosis Factor-alphaU937 CellsConceptsTrans-Golgi networkPlasma membraneTNF-R1Golgi regionConfocal immunofluorescence microscopyHuman endothelial cell line ECV304Endothelial cell line ECV304Receptor-mediated endocytosisAdaptor proteinSubcellular localizationSubcellular locationCell fractionationBovine aortic endothelial cellsCoimmunoprecipitation studiesEndothelial cellsTRADDCell line U937Golgi apparatusSubcellular interactionsWestern blot analysisCell extractsMonocyte cell line U937Expression plasmidGolgiImmunofluorescence microscopy
1998
Tumor necrosis factor is delivered to mitochondria where a tumor necrosis factor-binding protein is localized.
Ledgerwood EC, Prins JB, Bright NA, Johnson DR, Wolfreys K, Pober JS, O'Rahilly S, Bradley JR. Tumor necrosis factor is delivered to mitochondria where a tumor necrosis factor-binding protein is localized. Laboratory Investigation 1998, 78: 1583-9. PMID: 9881958.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAntibodies, MonoclonalCarrier ProteinsCells, CulturedHumansImmunohistochemistryIntracellular MembranesIodine RadioisotopesLysosomesMicroscopy, ImmunoelectronMitochondriaReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor Decoy ReceptorsTumor Necrosis Factor-alphaU937 CellsConceptsInner mitochondrial membraneExtracellular ligandsMitochondrial membraneTumor necrosis factor receptorIsolated mitochondriaBinding proteinNecrosis factor receptorMitochondriaCell surfaceImmunoelectron microscopyProteinFactor receptorSubcellular fractionsWestern blottingFactor binding proteinTNF effectsPathwayDiverse actionsExogenous TNFTNFR-IIMonoclonal antibodiesTumor necrosis factor binding proteinLysosomesTumor necrosis factorBlotting11 Tumour necrosis factor is trafficked to a mitochondrial tumour necrosis factor binding protein
Ledgerwood E, Prins J, Bright N, Johnson D, Wolfreys K, Pober J, O'Rahilly S, Bradley J. 11 Tumour necrosis factor is trafficked to a mitochondrial tumour necrosis factor binding protein. Biochemical Society Transactions 1998, 26: s316-s316. PMID: 10047830, DOI: 10.1042/bst026s316.Peer-Reviewed Original Research