2022
Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma
Al-Lamki RS, Wang J, Pober JS, Bradley JR. Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma. American Journal Of Pathology 2022, 192: 722-736. PMID: 35063404, DOI: 10.1016/j.ajpath.2021.12.010.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseCell cycle entryCcRCC cellsDeath receptor 3Protein kinaseClear cell renal cell carcinoma cellsProximity ligation assayRenal cell carcinoma cellsReceptor 3E-selectinPotential new targetsCycle entryNF-κB-dependent mannerNF-κBLigation assayTumor gradeCcRCC tissuesFunctional interactionSelectin expressionFunctional roleClear cell renal cell carcinomaOrgan cultureCell renal cell carcinomaExpression increasesAddition of TL1A
2020
Complement 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 ResearchConceptsMembrane 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
2016
Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice
Qin L, Li G, Kirkiles‐Smith N, Clark P, Fang C, Wang Y, Yu Z, Devore D, Tellides G, Pober J, Jane‐Wit D. Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice. American Journal Of Transplantation 2016, 16: 2865-2876. PMID: 27104811, PMCID: PMC5075274, DOI: 10.1111/ajt.13834.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryAllograft vasculopathyEndothelial cell activationReperfusion injuryCell activationComplement C5 inhibitionNuclear factor kappa BSolid organ transplantsT cell infiltrationTerminal complement activationVCAM-1 expressionComplement C5 activationFactor kappa BNeutrophil infiltrationHumanized miceDiffuse stenosisIntraluminal thrombosisArterial graftsC5 inhibitionCell infiltrationHumanized modelNeointimal hyperplasiaOrgan transplantsAlloantibodiesNF-kB
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 pathogenesis
2001
TNF 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 typesCells
2000
Caveolin-1 Associates with TRAF2 to Form a Complex That Is Recruited to Tumor Necrosis Factor Receptors*
Feng X, Gaeta M, Madge L, Yang J, Bradley J, Pober J. Caveolin-1 Associates with TRAF2 to Form a Complex That Is Recruited to Tumor Necrosis Factor Receptors*. Journal Of Biological Chemistry 2000, 276: 8341-8349. PMID: 11112773, DOI: 10.1074/jbc.m007116200.Peer-Reviewed Original ResearchConceptsCaveolin-1Confocal fluorescence microscopyIntracellular regionNecrosis factor receptor-associated factor 2TNF receptor 2Receptor-associated factor 2TNF receptor 1Promoter-reporter geneCaveolin-1 associatesFluorescence microscopyProtein caveolin-1Caveolin-1 proteinHuman embryonic kidney 293 cellsIntracellular adapter proteinEmbryonic kidney 293 cellsAbsence of ligandRegions of enrichmentKidney 293 cellsEndogenous TRAF2HEK-293 cellsAdapter proteinCultured human umbilical vein endothelial cellsHuman umbilical vein endothelial cellsPlasma membraneUmbilical vein endothelial cellsSelective Inhibition of NF-κB Activation by a Peptide That Blocks the Interaction of NEMO with the IκB Kinase Complex
May M, D'Acquisto F, Madge L, Glöckner J, Pober J, Ghosh S. Selective Inhibition of NF-κB Activation by a Peptide That Blocks the Interaction of NEMO with the IκB Kinase Complex. Science 2000, 289: 1550-1554. PMID: 10968790, DOI: 10.1126/science.289.5484.1550.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnti-Inflammatory Agents, Non-SteroidalCells, CulturedCOS CellsEndothelium, VascularE-SelectinGene Expression RegulationHeLa CellsHumansI-kappa B KinaseInflammationMiceMice, Inbred C57BLMolecular Sequence DataMutationNF-kappa BPeptidesPoint MutationProtein Serine-Threonine KinasesProtein Structure, TertiaryRecombinant Fusion ProteinsConceptsNF-kappaBBasal NF-kappaB activityExperimental mouse modelTranscription factor nuclear factorCytokine-induced NF-kappaB activationCell-permeable NBD peptideInhibitor of kappaBNF-κB activationNF-kappaB activityNF-kappaB activationAssociation of NEMOIKK complexAcute inflammationDevelopment of drugsProinflammatory activationInflammatory responseNBD peptideMouse modelProinflammatory stimuliIκB kinase (IKK) complexNuclear factorRegulatory protein NEMOInflammationSelective inhibitionExpression of genesA 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 productsTranscriptionKinasePhosphatidylinositolIL-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
1997
TNF initiates E-selectin transcription in human endothelial cells through parallel TRAF-NF-kappa B and TRAF-RAC/CDC42-JNK-c-Jun/ATF2 pathways.
Min W, Pober JS. TNF initiates E-selectin transcription in human endothelial cells through parallel TRAF-NF-kappa B and TRAF-RAC/CDC42-JNK-c-Jun/ATF2 pathways. The Journal Of Immunology 1997, 159: 3508-18. PMID: 9317150, DOI: 10.4049/jimmunol.159.7.3508.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 2Antigens, SurfaceCalcium-Calmodulin-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinE-SelectinEndothelium, VascularGTP-Binding ProteinsHumansJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein KinasesNF-kappa BPhosphorylationPromoter Regions, GeneticProto-Oncogene Proteins c-junRac GTP-Binding ProteinsReceptors, Tumor Necrosis FactorTranscription FactorsTranscription, GeneticTumor Necrosis Factor Receptor-Associated Peptides and ProteinsTumor Necrosis Factor-alphaUmbilical VeinsConceptsTransient overexpressionHuman endothelial cellsC-JunSelectin transcriptionATF2/c-JunN-terminalATF2 pathwayPromoter-reporter geneKappa B elementCAMP-responsive elementEndothelial cellsDomain phosphorylationEndogenous JNKAdaptor proteinInactive JNKNF-kappa BGene transcriptionGene promoterKappa BJNK activationKinase 1TranscriptionTRAF2 proteinCdc42JNK
1996
A Sustained Reduction in IκB-β May Contribute to Persistent NF-κB Activation in Human Endothelial Cells*
Johnson D, Douglas I, Jahnke A, Ghosh S, Pober J. A Sustained Reduction in IκB-β May Contribute to Persistent NF-κB Activation in Human Endothelial Cells*. Journal Of Biological Chemistry 1996, 271: 16317-16322. PMID: 8663191, DOI: 10.1074/jbc.271.27.16317.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCell Adhesion MoleculesCell MembraneCell NucleusCells, CulturedConsensus SequenceCytosolDNADNA-Binding ProteinsEndothelium, VascularGene ExpressionHistocompatibility Antigens Class IHumansI-kappa B ProteinsIntercellular Adhesion Molecule-1Interleukin-1KineticsMolecular Sequence DataNF-kappa BOligodeoxyribonucleotidesTetradecanoylphorbol AcetateTumor Necrosis Factor-alphaUmbilical VeinsVascular Cell Adhesion Molecule-1ConceptsAdhesion molecule-1Vascular cell adhesion molecule-1Intercellular adhesion molecule-1Cell adhesion molecule-1Phorbol myristate acetateInterleukin-1alphaNF-kappaB activationMolecule-1Sustained reductionNF-kappaBEndothelial cellsIkappaB-alphaIkappaB-betaHuman endothelial cellsHuman leukocyte antigen (HLA) class INF-kappaB.Inhibitory protein IkappaB-alphaCell surface molecule expressionIkappaB-beta degradationPersistent NF-κB activationSurface molecule expressionAntigen class INF-κB activationIkappaB-beta levelsDe novo expressionKinetically coordinated induction of TAP1 and HLA class I by IFN-gamma: the rapid induction of TAP1 by IFN-gamma is mediated by Stat1 alpha.
Min W, Pober JS, Johnson DR. Kinetically coordinated induction of TAP1 and HLA class I by IFN-gamma: the rapid induction of TAP1 by IFN-gamma is mediated by Stat1 alpha. The Journal Of Immunology 1996, 156: 3174-83. PMID: 8617938, DOI: 10.4049/jimmunol.156.9.3174.Peer-Reviewed Original ResearchAllelesATP Binding Cassette Transporter, Subfamily B, Member 2ATP-Binding Cassette TransportersBase SequenceCysteine EndopeptidasesDNA-Binding ProteinsEndopeptidasesExtracellular Matrix ProteinsGene Expression RegulationHeLa CellsHistocompatibility Antigens Class IHLA AntigensHLA-B AntigensHumansInterferon Regulatory Factor-1Interferon-gammaInterferon-Stimulated Gene Factor 3KineticsMacromolecular SubstancesMolecular Sequence DataNerve Tissue ProteinsNF-kappa BPhosphoproteinsPromoter Regions, GeneticRNA, MessengerTranscription FactorsTranscription, GeneticTranscriptional Regulation of the Interleukin-2 Gene in Normal Human Peripheral Blood T Cells CONVERGENCE OF COSTIMULATORY SIGNALS AND DIFFERENCES FROM TRANSFORMED T CELLS (∗)
Hughes C, Pober J. Transcriptional Regulation of the Interleukin-2 Gene in Normal Human Peripheral Blood T Cells CONVERGENCE OF COSTIMULATORY SIGNALS AND DIFFERENCES FROM TRANSFORMED T CELLS (∗). Journal Of Biological Chemistry 1996, 271: 5369-5377. PMID: 8621390, DOI: 10.1074/jbc.271.10.5369.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesBase SequenceBinding SitesCD3 ComplexCell Line, TransformedCell NucleusCells, CulturedFlow CytometryGene Expression RegulationHumansInterleukin-2KineticsLuciferasesLymphocyte ActivationMolecular Sequence DataNF-kappa BPromoter Regions, GeneticRecombinant ProteinsRegulatory Sequences, Nucleic AcidSignal TransductionT-LymphocytesTranscription FactorsTranscription, GeneticTransfectionTumor Cells, CulturedConceptsNormal T cellsT cellsCostimulatory signalsDifferent costimulatory signalsT cell receptorActivated T-cells (NFAT) sitesNormal human T cellsHuman T cellsT cell sitesTransformed T cellsCD2 antibodiesNF-kappaB siteAccessory cellsTumor cell linesCell receptorInterleukin-2 geneNuclear factorPrimary activationIL-2 promoterJurkat T cellsProximal AP-1 siteCell linesAntibodiesAP-1 siteTranscriptional regulation
1994
HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons.
Johnson DR, Pober JS. HLA class I heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons. Molecular And Cellular Biology 1994, 14: 1322-1332. PMID: 8289810, PMCID: PMC358487, DOI: 10.1128/mcb.14.2.1322.Peer-Reviewed Original ResearchBase SequenceBinding SitesCloning, MolecularConsensus SequenceDNA PrimersDNA-Binding ProteinsDrug SynergismGene ExpressionGenes, MHC Class IHeLa CellsHLA-B7 AntigenHumansInterferon-betaInterferon-gammaLymphotoxin-alphaMolecular Sequence DataNF-kappa BNuclear ProteinsPolymerase Chain ReactionPromoter Regions, GeneticRecombinant ProteinsSequence DeletionSequence Homology, Nucleic AcidTransfection