2018
DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation
Xiao Q, Wu J, Wang WJ, Chen S, Zheng Y, Yu X, Meeth K, Sahraei M, Bothwell ALM, Chen L, Bosenberg M, Chen J, Sexl V, Sun L, Li L, Tang W, Wu D. DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation. Nature Medicine 2018, 24: 262-270. PMID: 29431745, PMCID: PMC5840007, DOI: 10.1038/nm.4496.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis Coli ProteinBeta CateninCD8-Positive T-LymphocytesCell Line, TumorColorectal NeoplasmsCytotoxicity, ImmunologicGene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsIntestinal NeoplasmsKiller Cells, NaturalLow Density Lipoprotein Receptor-Related Protein-5MelanomaProgrammed Cell Death 1 ReceptorPTEN PhosphohydrolaseSignal TransductionSTAT5 Transcription FactorTumor Escape
2017
Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis
Chae W, Park J, Henegariu O, Yilmaz S, Hao L, Bothwell ALM. Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis. Immunology 2017, 152: 265-275. PMID: 28556921, PMCID: PMC5588763, DOI: 10.1111/imm.12766.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesAutoimmunityCell MembraneCell ProliferationCHO CellsColitisColonCricetulusDisease Models, AnimalDNA-Binding ProteinsForkhead Transcription FactorsGenetic Predisposition to DiseaseIntercellular Signaling Peptides and ProteinsLymphocyte ActivationMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesPhenotypeSelf ToleranceSignal TransductionTime FactorsT-Lymphocytes, RegulatoryTransfectionConceptsRegulatory T cellsTreg cellsDKK-1 expressionAutoimmune colitisDickkopf-1T cellsT cell-mediated toleranceEffector CD4 T cellsCD4 T cellsInduction of toleranceT cell proliferationT cell receptor stimulationNovel TregColitis modelImmunological homeostasisImmunological toleranceFoxp3Receptor stimulationCanonical Wnt pathwayColitisFunctional inhibitionMonoclonal antibodiesDe novo protein synthesisProtein kinase pathwaySuppressor function
2016
The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DermatophagoidesAntigens, ProtozoanAsthmaBlood PlateletsCell DifferentiationCells, CulturedCytokinesExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansInflammationIntercellular Signaling Peptides and ProteinsLeishmania majorLeishmaniasis, CutaneousMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicModels, AnimalPyroglyphidaeSignal TransductionTh2 CellsTOR Serine-Threonine KinasesWnt ProteinsConceptsCell-mediated inflammationTh2 cell cytokine productionCell cytokine productionLeukocyte-platelet aggregatesLeukocyte infiltrationDkk-1Cytokine productionT helper 2 cellsLeishmania major infectionHouse dust miteTranscription factor c-MafAllergen challengeMajor infectionDust miteImmune responseDickkopf-1Parasitic infectionsGATA-3Pathological roleFunctional inhibitionInflammationC-MafP38 MAPKInfiltrationInfection
2008
Interferon-γ Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation*
Bai Y, Ahmad U, Wang Y, Li JH, Choy JC, Kim RW, Kirkiles-Smith N, Maher SE, Karras JG, Bennett CF, Bothwell AL, Pober JS, Tellides G. Interferon-γ Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation*. Journal Of Biological Chemistry 2008, 283: 6832-6842. PMID: 18192275, DOI: 10.1074/jbc.m706021200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsApoptosisApoptosis Regulatory ProteinsF-Box ProteinsGene Expression RegulationHumansInterferon-gammaIntracellular Signaling Peptides and ProteinsMiceModels, BiologicalMuscle, Smooth, VascularNeoplasm ProteinsProto-Oncogene Proteins c-bcl-2Signal TransductionSTAT3 Transcription FactorTissue TransplantationConceptsVascular smooth muscle cellsInhibitor of apoptosisHuman vascular smooth muscle cellsSTAT3 activationNoxa expressionFactor 1Mouse vascular smooth muscle cellsExpression of XAF1Vascular smooth muscle cell apoptosisSmooth muscle cell apoptosisMuscle cell apoptosisApoptotic stimuliTranscription factorsTranscription (STAT) proteinsGene productsPro-apoptotic effectsHuman coronary artery graftsSignal transducerDeath receptorsMicroarray analysisHuman endothelial cellsChimeric animal modelPhenotypic modulationSTAT1 activationNuclear translocation
2006
Manganese Treatment Modulates the Expression of Peroxisome Proliferator-activated Receptors in Astrocytoma and Neuroblastoma Cells
Isaac AO, Kawikova I, Bothwell AL, Daniels CK, Lai JC. Manganese Treatment Modulates the Expression of Peroxisome Proliferator-activated Receptors in Astrocytoma and Neuroblastoma Cells. Neurochemical Research 2006, 31: 1305-1316. PMID: 17053972, DOI: 10.1007/s11064-006-9173-0.Peer-Reviewed Original ResearchConceptsPeroxisome proliferator-activated receptorMn neurotoxicityPPAR isoformsExpression of PPARsNeuroblastoma cellsProliferator-activated receptorAnti-oxidant responseCell typesChronic exposureNeurotoxic mechanismsPeroxisome proliferatorPathophysiological importanceHuman astrocytomasNeural cellsNeurotoxicityManganese chloride treatmentProtein expressionCell proliferationAstrocytomasManganese treatmentReceptorsMolecular mechanismsTreatmentCytosolic fractionCells
2004
Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase
Fernandez-Cabezudo MJ, Vijayasarathy C, Pflugh DL, Bothwell AL, al-Ramadi BK. Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase. International Immunology 2004, 16: 1215-1223. PMID: 15237112, DOI: 10.1093/intimm/dxh124.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteClone CellsHumansInterleukin-4Lectins, C-TypeLeukosialinLymphocyte ActivationLymphocyte Specific Protein Tyrosine Kinase p56(lck)MiceMultiprotein ComplexesPhosphoproteinsPhosphorylationReceptors, Interleukin-2Shc Signaling Adaptor ProteinsSialoglycoproteinsSignal TransductionSrc Homology 2 Domain-Containing, Transforming Protein 1Th2 CellsConceptsCD43 ligationSLP-76Adaptor protein SLP-76Tyrosine kinaseLck-deficient cellsTyrosine phosphorylated proteinsLck tyrosine kinaseMulti-component complexesT cell biologyNaive splenic T cellsPhosphorylated proteinsMajor protein bandsTyrosine phosphorylationCell biologyPathway componentsDifferential requirementExact functionDifferent effector functionsPhosphorylationT cell moleculesCellular proliferationProtein bandsCell moleculesLckKinaseInterferon α but Not Interleukin 12 Activates STAT4 Signaling in Human Vascular Endothelial Cells*
Torpey N, Maher SE, Bothwell AL, Pober JS. Interferon α but Not Interleukin 12 Activates STAT4 Signaling in Human Vascular Endothelial Cells*. Journal Of Biological Chemistry 2004, 279: 26789-26796. PMID: 15087447, DOI: 10.1074/jbc.m401517200.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCells, CulturedChemokine CCL2DNADNA, ComplementaryDNA-Binding ProteinsDose-Response Relationship, DrugEndothelium, VascularEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoblottingInflammationInterferon-alphaInterleukin-12Oligonucleotide Array Sequence AnalysisPhosphorylationPrecipitin TestsProtein Structure, TertiaryRecombinant ProteinsRepressor ProteinsRetroviridaeReverse Transcriptase Polymerase Chain ReactionRNARNA, MessengerSignal TransductionSTAT4 Transcription FactorSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsTime FactorsTrans-ActivatorsTranscription FactorsUmbilical VeinsUp-RegulationConceptsHuman umbilical vein ECMonocyte chemoattractant protein-1Quantitative RT-PCRVascular endothelial cellsEndothelial cellsChemokine monocyte chemoattractant protein-1Chemoattractant protein-1Cultured human umbilical vein endothelial cellsPro-inflammatory behaviorIFNalpha responseHuman vascular endothelial cellsHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsNeuroblastoma cell linesSuppressor of cytokineVein endothelial cellsEffector cellsInterleukin-12T cellsSTAT4 pathwayInterferon αIL12 receptorCytokinesU3A cellsRT-PCR
2002
Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction
Shim JH, Lee HK, Chang EJ, Chae WJ, Han JH, Han DJ, Morio T, Yang JJ, Bothwell A, Lee SK. Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 10617-10622. PMID: 12149481, PMCID: PMC124991, DOI: 10.1073/pnas.162522099.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntifungal AgentsApoptosisCaspase 3Caspase 9CaspasesCell DivisionCyclosporineFuransHeart TransplantationHeLa CellsHumansImmunosuppressive AgentsJurkat CellsLipidsLymphocyte ActivationMolecular StructurePhosphorylationPoly(ADP-ribose) PolymerasesProto-Oncogene Proteins c-bcl-2RatsRats, Inbred LewRats, WistarReceptor-CD3 Complex, Antigen, T-CellSignal TransductionT-LymphocytesTyrosine