2023
Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire
Yarovinsky T, Su M, Chen C, Xiang Y, Tang W, Hwa J. Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire. Seminars In Immunology 2023, 69: 101809. PMID: 37478801, PMCID: PMC10528349, DOI: 10.1016/j.smim.2023.101809.Peer-Reviewed Original ResearchConceptsPost-translational modificationsAcute cardiovascular eventsChronic cardiovascular diseaseCardiovascular diseaseSmall molecule inhibitorsPyroptosis resultsGenetic toolsGasdermin proteinsWhole organismInflammatory caspasesCardiovascular eventsCell deathMolecule inhibitorsCell typesProteolytic cleavageCellular mechanismsActivation of inflammasomesCardiovascular systemKnockout animalsAmplification of inflammationRole of pyroptosisPro-inflammatory processesDifferent cellsNovel therapeutic approachesPyroptosis
2022
Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growth
2020
Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis
Zhang Y, Wang Y, Zhang L, Xia L, Zheng M, Zeng Z, Liu Y, Yarovinsky T, Ostriker AC, Fan X, Weng K, Su M, Huang P, Martin KA, Hwa J, Tang WH. Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis. Circulation Research 2020, 127: 855-873. PMID: 32597702, PMCID: PMC7486265, DOI: 10.1161/circresaha.120.316951.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAnimalsBlood PlateletsCase-Control StudiesCells, CulturedChildChild, PreschoolCoronary Artery DiseaseCoronary VesselsDisease Models, AnimalFemaleHumansInfantMaleMice, Inbred C57BLMice, KnockoutMicroRNAsMucocutaneous Lymph Node SyndromeMuscle, Smooth, VascularMyocytes, Smooth MusclePlatelet ActivationProspective StudiesReceptor, Platelet-Derived Growth Factor betaSeverity of Illness IndexSignal TransductionYoung AdultConceptsSevere coronary pathologyCoronary artery pathologyKawasaki diseaseCoronary pathologyArtery pathologyMiR-223Medial damageHealthy controlsVSMC dedifferentiationHallmark of KDMiR-223 knockout miceVascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationPlatelet miR-223Platelet-derived miRNAsVSMC differentiationMedial elastic fibersMiR-223 levelsMuscle cell dedifferentiationPotential therapeutic strategyInhibitor imatinib mesylateVascular smooth muscle cell phenotypeSmooth muscle cell phenotypeMiR-223 mimicsUptake of platelets
2018
T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K
Rao GK, Wong A, Collinge M, Sarhan J, Yarovinsky TO, Ramgolam VS, Gaestel M, Pardi R, Bender JR. T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K. PLOS ONE 2018, 13: e0201103. PMID: 30048492, PMCID: PMC6065199, DOI: 10.1371/journal.pone.0201103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Culture TechniquesCytoplasmELAV-Like Protein 1Heterogeneous-Nuclear RibonucleoproteinsHumansIntracellular Signaling Peptides and ProteinsJurkat CellsLymphocyte Function-Associated Antigen-1Mice, Inbred C57BLMice, KnockoutProtein Serine-Threonine KinasesProteomeRNA StabilityRNA, MessengerSignal TransductionT-LymphocytesConceptsKinase MK2Β2-integrin lymphocyte function-associated antigen-1AU-rich elementsLymphocyte function-associated antigen-1Integrin lymphocyte function-associated antigen-1HuR localizationProtein HuR.Key regulatorMRNA stabilizationCritical activatorCytoplasmic translocationHuR activitySequential activationHuRIntricate processFunction-associated antigen-1MRNAEngagement resultsMK2Antigen 1H1ActivationHnRNPsHuR.Transcripts
2014
Chemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis
Morrison AR, Yarovinsky TO, Young BD, Moraes F, Ross TD, Ceneri N, Zhang J, Zhuang ZW, Sinusas AJ, Pardi R, Schwartz MA, Simons M, Bender JR. Chemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis. Journal Of Experimental Medicine 2014, 211: 1957-1968. PMID: 25180062, PMCID: PMC4172219, DOI: 10.1084/jem.20132130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriesCD18 AntigensDNA PrimersFlow CytometryHumansMiceMice, Inbred C57BLMonocytesNeovascularization, PhysiologicNonmuscle Myosin Type IIARac GTP-Binding ProteinsReal-Time Polymerase Chain ReactionReceptors, CCR2RNA StabilityVascular Endothelial Growth Factor AX-Ray MicrotomographyConceptsMyosin IIASignal transduction eventsHuR translocationRapid nuclearTransduction eventsProteomic analysisProtein HuR.Induction of arteriogenesisMRNA stabilityMRNA stabilizationNovel roleCytosolic translocationMyosin-9ICAM-1 adhesionReceptor engagementDevelopmental vasculogenesisCellular effectorsMolecular triggersTranslocationHeavy chainGrowth factorMyeloid cellsVascular endothelial growth factorKey molecular triggerCCL2 stimulationCeramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis
Mehra VC, Jackson E, Zhang XM, Jiang XC, Dobrucki LW, Yu J, Bernatchez P, Sinusas AJ, Shulman GI, Sessa WC, Yarovinsky TO, Bender JR. Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis. American Journal Of Pathology 2014, 184: 1562-1576. PMID: 24606881, PMCID: PMC4005977, DOI: 10.1016/j.ajpath.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaArteriesCattleCeramidesDiet, High-FatEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHaploinsufficiencyHindlimbHumansIschemiaMice, Inbred C57BLNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPalmitic AcidPhosphorylationProtein Phosphatase 2Proto-Oncogene Proteins c-aktSerine C-PalmitoyltransferaseSignal TransductionVascular Endothelial Growth Factor AConceptsPP2A inhibitor okadaic acidProtein phosphatase 2AInhibitor okadaic acidVEGF-induced signalingSerine palmitoyltransferase inhibitor myriocinDe novo ceramide synthesisPhosphatase 2AENOS agonistsNovo ceramide synthesisPalmitic acidAngiogenic responsePotential molecular targetsOkadaic acidEndothelial cellsEarly speciesEndothelial cell responsesCord formationVEGFR2 phosphorylationSaturated free fatty acidVEGF resistanceCeramide synthesisResistance mechanismsMolecular targetsVascular homeostasisPhosphorylation
2012
Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING
Holm CK, Jensen SB, Jakobsen MR, Cheshenko N, Horan KA, Moeller HB, Gonzalez-Dosal R, Rasmussen SB, Christensen MH, Yarovinsky TO, Rixon FJ, Herold BC, Fitzgerald KA, Paludan SR. Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nature Immunology 2012, 13: 737-743. PMID: 22706339, PMCID: PMC3411909, DOI: 10.1038/ni.2350.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell FusionChemokine CXCL10HEK293 CellsHeLa CellsHerpesvirus 1, HumanHumansImmunity, InnateInterferon Type ILeukocytesLymphocyte ActivationMacrophagesMembrane FusionMembrane GlycoproteinsMembrane ProteinsMiceMice, KnockoutMyeloid Differentiation Factor 88Signal TransductionToll-Like Receptor 7Toll-Like Receptor 9Virus InternalizationMacrophage β2 Integrin–Mediated, HuR-Dependent Stabilization of Angiogenic Factor–Encoding mRNAs in Inflammatory Angiogenesis
Zhang J, Modi Y, Yarovinsky T, Yu J, Collinge M, Kyriakides T, Zhu Y, Sessa WC, Pardi R, Bender JR. Macrophage β2 Integrin–Mediated, HuR-Dependent Stabilization of Angiogenic Factor–Encoding mRNAs in Inflammatory Angiogenesis. American Journal Of Pathology 2012, 180: 1751-1760. PMID: 22322302, PMCID: PMC3349897, DOI: 10.1016/j.ajpath.2011.12.025.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAnimalsCD18 AntigensCell AdhesionCells, CulturedDisease Models, AnimalELAV ProteinsGene Expression RegulationGene Knockout TechniquesHindlimbInflammationIschemiaMacrophagesMiceMice, KnockoutMuscle, SkeletalNeovascularization, PathologicReal-Time Polymerase Chain ReactionRNA, MessengerConceptsKnockout miceAngiogenic factorsT cell cytokine productionIntercellular adhesion molecule-1Blood flow recoveryFemoral artery ligationLittermate wild-type controlsVascular endothelial growth factorBone marrow-derived macrophagesMatrix metalloproteinase-9Adhesion molecule-1Endothelial growth factorMarrow-derived macrophagesSoluble factor productionWild-type controlsArtery ligationLigand intercellular adhesion molecule-1Cytokine productionInflammatory angiogenesisMetalloproteinase-9Tissue ischemiaInflammatory stimuliMolecule-1Macrophage productionNeovascular responsePhospholipid Scramblase 1 Mediates Type I Interferon-Induced Protection against Staphylococcal α-Toxin
Lizak M, Yarovinsky TO. Phospholipid Scramblase 1 Mediates Type I Interferon-Induced Protection against Staphylococcal α-Toxin. Cell Host & Microbe 2012, 11: 70-80. PMID: 22264514, PMCID: PMC3266557, DOI: 10.1016/j.chom.2011.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBacterial ToxinsBody TemperatureBody WeightCell LineCell SurvivalDisease Models, AnimalEpithelial CellsHemolysin ProteinsHumansInterferon-alphaLipoylationMiceMice, KnockoutPhospholipid Transfer ProteinsProtein Processing, Post-TranslationalStaphylococcal InfectionsStaphylococcus aureusSurvival AnalysisConceptsLung epithelial cellsI interferonΑ-toxinStaphylococcal α-toxinCytolytic activityPhospholipid scramblase 1Epithelial cellsInnate protective mechanismsCause of pneumoniaHuman lung epithelial cellsType I interferonAureus clinical isolatesPore-forming toxinsMajor virulence factorScramblase 1Intracellular ATP depletionPositive pathogen Staphylococcus aureusMice displayClinical isolatesAureus strainsProtective mechanismCellular depletionBacterial pore-forming toxinsVirulence factorsUnderlying mechanism
2006
Early Exposure to IL-4 Stabilizes IL-4 mRNA in CD4+ T Cells via RNA-Binding Protein HuR
Yarovinsky TO, Butler NS, Monick MM, Hunninghake GW. Early Exposure to IL-4 Stabilizes IL-4 mRNA in CD4+ T Cells via RNA-Binding Protein HuR. The Journal Of Immunology 2006, 177: 4426-4435. PMID: 16982877, DOI: 10.4049/jimmunol.177.7.4426.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceBase SequenceCD4-Positive T-LymphocytesELAV ProteinsELAV-Like Protein 1Electrophoretic Mobility Shift AssayFlow CytometryFluorescent Antibody TechniqueGene ExpressionGene Expression RegulationImmunoblottingInterleukin-4Lymphocyte ActivationMiceMicroscopy, ConfocalMolecular Sequence DataProtein Structure, SecondaryRNA StabilityRNA, MessengerRNA-Binding Proteins
2005
Increased Sensitivity to Staphylococcal Enterotoxin B following Adenoviral Infection
Yarovinsky TO, Mohning MP, Bradford MA, Monick MM, Hunninghake GW. Increased Sensitivity to Staphylococcal Enterotoxin B following Adenoviral Infection. Infection And Immunity 2005, 73: 3375-3384. PMID: 15908364, PMCID: PMC1111844, DOI: 10.1128/iai.73.6.3375-3384.2005.Peer-Reviewed Original ResearchConceptsStaphylococcal enterotoxin BAdenoviral infectionEnterotoxin BStaphylococcal enterotoxin B exposureD-galactosamine sensitizationSystemic adenoviral infectionIncreased sensitivityPrime miceMajor virulence factorLiver injuryProfound hypothermiaStaphylococcal diseaseMurine modelGamma interferonKnockout miceB exposureToxic shockInfectionStaphylococcal enterotoxinsMiceVirulence factorsIncreased productionExposureHypothermiaInjury
2001
Lung fibroblasts inhibit activation-induced death of T cells through PGE2-dependent mechanisms
Yarovinsky T, Hunninghake G. Lung fibroblasts inhibit activation-induced death of T cells through PGE2-dependent mechanisms. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2001, 281: l1248-l1256. PMID: 11597917, DOI: 10.1152/ajplung.2001.281.5.l1248.Peer-Reviewed Original ResearchConceptsActivation-induced cell deathFibroblast-conditioned mediumT cellsLung fibroblastsFas/Fas ligand-dependent mechanismFas ligand-dependent mechanismMouse primary lung fibroblastsPGE2-dependent mechanismsImmobilized anti-CD3 antibodyAnti-CD3 antibodyActivation-induced deathPrimary lung fibroblastsLigand-dependent mechanismTreatment of fibroblastsCaspase-3Fas receptorAntiapoptotic activityIndomethacinCell deathInhibitory activityFibroblastsDeathFibroblast culturesCaspase-8Cells
2000
Application of DNA Topoisomerase-Activated Adapters to Riboprobe Synthesis
Yarovinsky T. Application of DNA Topoisomerase-Activated Adapters to Riboprobe Synthesis. BioTechniques 2000, 28: 1160-1165. PMID: 10868281, DOI: 10.2144/00286st06.Peer-Reviewed Original ResearchExpression of the protein tyrosine phosphatase, phosphatase of regenerating liver 1, in the outer segments of primate cone photoreceptors
Yarovinsky T, Rickman D, Diamond R, Taub R, Hageman G, Rickman C. Expression of the protein tyrosine phosphatase, phosphatase of regenerating liver 1, in the outer segments of primate cone photoreceptors. Brain Research 2000, 77: 95-103. PMID: 10814835, DOI: 10.1016/s0169-328x(00)00045-0.Peer-Reviewed Original ResearchConceptsProtein tyrosine phosphatasePRL-1 genePRL-1Regenerating Liver-1Tyrosine phosphataseSingle mRNA speciesAmino acid sequencePRL-1 mRNAPrimate cone photoreceptorsPhotoreceptor cell functionImmediate early genesUnique transcriptsCone photoreceptor cellsCone photoreceptorsCDNA clonesMRNA speciesAcid sequenceAffinity-purified antibodiesOuter segmentsEarly genesSouthern blotGenesHigh abundanceChromosome 6qPhosphatase activity