2021
Cardiac allograft vasculopathy: current review and future research directions
Pober JS, Chih S, Kobashigawa J, Madsen JC, Tellides G. Cardiac allograft vasculopathy: current review and future research directions. Cardiovascular Research 2021, 117: 2624-2638. PMID: 34343276, PMCID: PMC8783389, DOI: 10.1093/cvr/cvab259.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyAllograft vasculopathyImmune-mediated vasculopathyLate graft lossGraft lossCardiac transplantationOrgan graftsTransplanted heartsCurrent therapiesVascular remodellingVasculopathyMajor causeCurrent reviewRemodellingTransplantationPathogenesisGraftTherapyPerfusionIncidenceDiagnosisVasculatureTumor 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
2020
Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesisComplement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells
Xie CB, Jiang B, Qin L, Tellides G, Kirkiles-Smith NC, Jane-wit D, Pober JS. Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells. Journal Of Clinical Investigation 2020, 130: 3437-3452. PMID: 32191642, PMCID: PMC7324183, DOI: 10.1172/jci135060.Peer-Reviewed Original ResearchConceptsIL-15/IL-15Rα complexesIL-1βHuman endothelial cellsMembrane attack complexEndothelial cellsAcute rejectionT cellsT cell-mediated acute rejectionCell-mediated acute rejectionComplement-mediated pathologiesIL-15Rα expressionGraft endothelial cellsHuman coronary artery graftsEffector memory CD4T cell infiltrationCoronary artery graftsIL-1 receptorActive IL-1βCultured human endothelial cellsNLRP3 inflammasome assemblyNoncanonical NF-κBArtery graftAlloreactive CD8Complement membrane attack complexMemory CD4Complement Membrane Attack Complex New Roles, Mechanisms of Action, and Therapeutic Targets
Xie CB, Jane-Wit D, Pober JS. Complement Membrane Attack Complex New Roles, Mechanisms of Action, and Therapeutic Targets. American Journal Of Pathology 2020, 190: 1138-1150. PMID: 32194049, PMCID: PMC7280757, DOI: 10.1016/j.ajpath.2020.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsComplement ActivationComplement Membrane Attack ComplexHumansImmunity, InnateInterleukinsNF-kappa BSignal TransductionConceptsMembrane attack complexMAC assemblyExpression of inhibitorMechanism of actionFacilitate secretionDependent transcriptionPlasma membraneIntracellular signalingComplement membrane attack complexAbsence of lysisSignalingRecent insightsBiophysical propertiesComplement-mediated diseasesAttack complexTherapeutic targetCell activationDisease pathogenesisAdaptive immunityNew roleIL-18IL-1βCytolytic effectorsProinflammatory effectsProinflammatory proteins
2019
Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Liu L, Fang C, Fu W, Jiang B, Li G, Qin L, Rosenbluth J, Gong G, Xie CB, Yoo P, Tellides G, Pober JS, Jane-Wit D. Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production. Circulation 2019, 141: 464-478. PMID: 31744330, PMCID: PMC7035199, DOI: 10.1161/circulationaha.119.042501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDelayed Graft FunctionFemaleGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansImmunoglobulin MInflammasomesInterleukin-18Interleukin-18 Receptor alpha SubunitIsoantibodiesMiceMice, SCIDOrgan TransplantationReperfusion InjurySignal TransductionT-Lymphocytes, Helper-InducerConceptsIschemia-reperfusion injuryDonor-specific antibodiesPeripheral helper cellsIL-18Helper cellsReperfusion injuryInterleukin-18IL-18R1Donor-specific antibody formationEndothelial cellsDelayed graft functionLate allograft lossT cell populationsAlloantibody productionAllograft lossChronic rejectionGraft functionClinical manifestationsPD-L2Antibody formationHumanized modelAllograft tissueImmunoglobulin MPatient specimensComplement activationEndothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retention
2015
Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+NIK+ signalosome on Rab5+ endosomes
Jane-wit D, Surovtseva YV, Qin L, Li G, Liu R, Clark P, Manes TD, Wang C, Kashgarian M, Kirkiles-Smith NC, Tellides G, Pober JS. Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+NIK+ signalosome on Rab5+ endosomes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 9686-9691. PMID: 26195760, PMCID: PMC4534258, DOI: 10.1073/pnas.1503535112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviral IAP Repeat-Containing 3 ProteinClathrinComplement Membrane Attack ComplexCoronary VesselsEndocytosisEndosomesEnzyme StabilityFlow CytometryHuman Umbilical Vein Endothelial CellsHumansHydrazonesInhibitor of Apoptosis ProteinsMice, SCIDNF-kappa BProtein BiosynthesisProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRab5 GTP-Binding ProteinsRNA, Small InterferingSecretory VesiclesSignal TransductionTNF Receptor-Associated Factor 3Ubiquitin-Protein LigasesConceptsNF-κB-inducing kinaseMembrane attack complexNoncanonical NF-κBGenome-wide siRNA screenComplement membrane attack complexNIK stabilizationDynamin-dependent mannerNoncanonical NF-κB signalingEndothelial cellsActive Rab5Attack complexSiRNA screenNF-κBAkt activationCytokine-mediated activationNF-κB signalingIκB kinaseSignalosomeRab5EndosomesKinaseAktInternalizationCoronary endothelial cellsActivationTumor 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
2013
Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells
Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS. Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells. Circulation 2013, 128: 2504-2516. PMID: 24045046, PMCID: PMC3885874, DOI: 10.1161/circulationaha.113.002972.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyPanel reactive antibodyNuclear factor-κB signalingFactor-κB signalingAllograft vasculopathyT cellsEndothelial cellsMembrane attack complexAlloreactive T cell activationChronic antibody-mediated rejectionNoncanonical nuclear factorProinflammatory gene programAntibody-mediated rejectionDonor-specific antibodiesGraft endothelial cellsLate allograft lossAlloreactive T cellsAllogeneic endothelial cellsT cell activationAttack complexHuman T cellsAllograft lossHeart transplantationTransplantation patientsLesion pathogenesisPericytes modulate endothelial sprouting
Chang WG, Andrejecsk JW, Kluger MS, Saltzman WM, Pober JS. Pericytes modulate endothelial sprouting. Cardiovascular Research 2013, 100: 492-500. PMID: 24042014, PMCID: PMC3826704, DOI: 10.1093/cvr/cvt215.Peer-Reviewed Original ResearchMeSH KeywordsBecaplerminCoculture TechniquesCulture Media, ConditionedHepatocyte Growth FactorHuman Umbilical Vein Endothelial CellsHumansMicrovesselsNeovascularization, PhysiologicParacrine CommunicationPericytesProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-sisSignal TransductionSpheroids, CellularTime FactorsTransfectionVascular Endothelial Growth Factor A
2009
Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death
Choy JC, Pober JS. Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death. American Journal Of Transplantation 2009, 9: 2281-2291. PMID: 19663890, PMCID: PMC3505447, DOI: 10.1111/j.1600-6143.2009.02771.x.Peer-Reviewed Original ResearchConceptsHuman CD8 T cellsCD8 T cellsInducible NO synthaseT cellsActivated T cellsNitric oxideDeprivation-induced cell deathCell deathAllogeneic endothelial cellsT cell proliferationActivation-induced cell deathCytokine deprivationGeneration of NOT cell deathExogenous nitric oxideHuman T cellsNO augmentsAllogeneic responseS-nitrosylationNO synthaseProtective effectActivity of caspasesEndothelial cellsPharmacological inhibitorsDeath
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 ResearchConceptsTumor necrosis factorCytolytic T lymphocytesEC injuryEndothelial cellsReactive oxygen speciesEndothelial cell dysfunctionMacrophage-derived cytokinesVascular endothelial cellsEndothelial dysfunctionNecrosis factorCell dysfunctionT lymphocytesInjuryCommon mediatorInflammationDysfunctionDeathOxygen speciesCytokinesLymphocytesNeutrophilsDifferent agentsBiochemical pathways
2001
Tumor necrosis factor receptor-associated factors (TRAFs)
Bradley J, Pober J. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene 2001, 20: 6482-6491. PMID: 11607847, DOI: 10.1038/sj.onc.1204788.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAmino Acid MotifsAnimalsHumansInterleukin-1Protein BindingProtein Structure, TertiaryProteinsReceptors, Tumor Necrosis FactorSignal TransductionTNF Receptor-Associated Factor 1TNF Receptor-Associated Factor 2TNF Receptor-Associated Factor 3TNF Receptor-Associated Factor 4TNF Receptor-Associated Factor 5TNF Receptor-Associated Factor 6Transcription Factor AP-1Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsConceptsTRAF proteinsNecrosis factor receptor-associated factorReceptor-associated factorZinc finger motifsToll/interleukinTumor necrosis factor receptor familyTRAFs 2Finger motifTRAF domainAdaptor proteinCytoplasmic domainFactor receptor familyHomology regionTRAF familyRegulated fashionDownstream eventsSignal transducerCellular responsesCell deathImportant regulatorReceptor familyProteinPathological processesNF-κBDiseased tissuesTNF 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 typesCellsInterleukin-11 Up-Regulates Survivin Expression in Endothelial Cells through a Signal Transducer and Activator of Transcription-3 Pathway
Mahboubi K, Li F, Plescia J, Kirkiles-Smith N, Mesri M, Du Y, Carroll J, Elias J, Altieri D, Pober J. Interleukin-11 Up-Regulates Survivin Expression in Endothelial Cells through a Signal Transducer and Activator of Transcription-3 Pathway. Laboratory Investigation 2001, 81: 327-334. PMID: 11310826, DOI: 10.1038/labinvest.3780241.Peer-Reviewed Original ResearchMeSH KeywordsDNA-Binding ProteinsEndothelium, VascularGene ExpressionHumansInhibitor of Apoptosis ProteinsInterleukin-11Microtubule-Associated ProteinsNeoplasm ProteinsPhosphorylationProteinsRNA, MessengerSerineSignal TransductionSTAT1 Transcription FactorSTAT3 Transcription FactorSurvivinTrans-ActivatorsTranscription, GeneticTransgenesUmbilical VeinsConceptsSignal transducerProtein kinase B/AktDominant-negative STAT3 mutantActivator of transcriptionSurvivin mRNA expressionTranscription 3 (STAT3) pathwayIL-11Survivin protein expressionSTAT3 mutantStimulation of serumProtein expression levelsSurvivin inductionSurvivin expressionAntiapoptotic proteinsInduces expressionMRNA expressionExpression levelsSurvivin proteinProtein expressionCritical mediatorMaximal inductionExpressionSurvivin mRNAProteinDose-dependent manner
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 actionIL-11 Activates Human Endothelial Cells to Resist Immune-Mediated Injury
Mahboubi K, Biedermann B, Carroll J, Pober J. IL-11 Activates Human Endothelial Cells to Resist Immune-Mediated Injury. The Journal Of Immunology 2000, 164: 3837-3846. PMID: 10725745, DOI: 10.4049/jimmunol.164.7.3837.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDCells, CulturedComplement System ProteinsCytokine Receptor gp130Cytotoxicity, ImmunologicDNA-Binding ProteinsDose-Response Relationship, ImmunologicEndothelium, VascularEnzyme ActivationHumansImmunity, InnateInflammation MediatorsInterleukin-11Interleukin-11 Receptor alpha SubunitMembrane GlycoproteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNF-kappa BPhosphorylationReceptors, InterleukinReceptors, Interleukin-11Signal TransductionSTAT1 Transcription FactorSTAT3 Transcription FactorT-Lymphocytes, CytotoxicTrans-ActivatorsTyrosineUmbilical VeinsConceptsIL-11Mitogen-activated protein kinaseP44 mitogen-activated protein kinaseImmune-Mediated InjuryCytolytic T lymphocytesNF-kappaB activationGp130-signaling cytokinesInflammatory injuryHuman endothelial cellsIL-11 receptorProinflammatory responseMolecule expressionT lymphocytesICAM-1Maximal responseE-selectinMHC AbsVivo modelNF-kappaBEndothelial cellsTyrosine phosphorylationPhospho-STAT3Cultured HUVECsInjuryKinase 1 inhibitor
1999
Human endothelial cells augment early CD40 ligand expression in activated CD4+ T cells through LFA-3-mediated stabilization of mRNA.
Murakami K, Ma W, Fuleihan R, Pober J. Human endothelial cells augment early CD40 ligand expression in activated CD4+ T cells through LFA-3-mediated stabilization of mRNA. The Journal Of Immunology 1999, 163: 2667-73. PMID: 10453007, DOI: 10.4049/jimmunol.163.5.2667.Peer-Reviewed Original ResearchConceptsCD40 ligand expressionT cellsCD40L mRNALFA-3CD40L expressionICAM-1Ligand expressionICAM-1 antisense oligonucleotideT-cell mRNA expressionCD40L protein expressionPretreatment of ECPromoter-reporter geneHuman endothelial cellsIL-2CD4Capacity of ECMRNA expressionICAM-2Endothelial cellsProtein expressionCD40LAntisense oligonucleotidePHAMRNACellsRecent 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 Research