2022
Preclinical development of an EP2 antagonist for post-seizure cognitive deficits
Varvel N, Amaradhi R, Espinosa-Garcia C, Duddy S, Franklin R, Banik A, Alemán-Ruiz C, Blackmer-Raynolds L, Wang W, Honore T, Ganesh T, Dingledine R. Preclinical development of an EP2 antagonist for post-seizure cognitive deficits. Neuropharmacology 2022, 224: 109356. PMID: 36460083, PMCID: PMC9894535, DOI: 10.1016/j.neuropharm.2022.109356.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCognitionCyclooxygenase 2EpilepsyInflammationMiceQuality of LifeRatsReceptors, Prostaglandin E, EP2 SubtypeSeizuresStatus EpilepticusConceptsCognitive deficitsStatus epilepticusY-maze performanceInvestigational new drugEP2 antagonistComorbidities of epilepsyReduced delayed mortalityY-mazeCognitive comorbiditiesBlood-brain barrier leakageDays of oral administrationCOX-2 inductionSigns of toxicityDeficitsIn vitro studiesEP2 receptorReceptor modulatorsDose linearityProstaglandin E2Neuronal injuryPreclinical developmentOral administrationPreventive treatmentHistopathological signsCyclooxygenase-2
2021
Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: a minimal ancestral deciduogenic signal†
Stadtmauer DJ, Wagner G. Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: a minimal ancestral deciduogenic signal†. Biology Of Reproduction 2021, 106: 155-172. PMID: 34591094, PMCID: PMC8757638, DOI: 10.1093/biolre/ioab183.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCell Line, TransformedCells, CulturedCyclic AMPCyclic AMP-Dependent Protein KinasesDeciduaDinoprostoneEndometriumFemaleFibroblastsGene ExpressionGenome-Wide Association StudyHumansMedroxyprogesterone AcetatePregnancyReceptors, Prostaglandin E, EP2 SubtypeSequence Analysis, RNASingle-Cell AnalysisConceptsPlacental mammalsCore gene regulatory networkCyclic AMP/protein kinase A (cAMP/PKA) pathwayProtein kinase A (PKA) pathwaySenescence-associated genesProgesterone-dependent activationGenome-wide studiesSingle-cell transcriptomicsGene regulatory networksProgesterone-dependent inductionMembrane-permeable cAMPKinase A PathwaySingle-cell analysisUse of PGE2Outgroup taxaCellular statesRegulatory networksPKA axisGene expressionDecidual genesPKA activationPGE2 receptor 2Progestin-dependent inductionA PathwayAdenylyl cyclase activationHunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice
Varela L, Stutz B, Song JE, Kim JG, Liu ZW, Gao XB, Horvath TL. Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward auto-activation loop in mice. Journal Of Clinical Investigation 2021, 131 PMID: 33848272, PMCID: PMC8121506, DOI: 10.1172/jci144239.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsAstrocytesHungerHypothalamusMaleMiceMice, TransgenicNeuronal PlasticityNeuronsReceptors, Prostaglandin E, EP2 SubtypeConceptsAgRP neuronsHypothalamic feeding circuitsInhibitory neurotransmitter GABAGhrelin administrationInhibitory toneAstrocytic responseMetabolic milieuProstaglandin E2Neurotransmitter GABANeuronal controlSynaptic plasticityGlial processesNeuronsNeural excitationMitochondrial adaptationsFood deprivationAstrocytesPerikaryaFeeding circuitRegion crucialFeedingObesityGABAExcitabilityChemogenetics
2020
Peripheral Myeloid Cell EP2 Activation Contributes to the Deleterious Consequences of Status Epilepticus
Varvel N, Espinosa-Garcia C, Hunter-Chang S, Chen D, Biegel A, Hsieh A, Blackmer-Raynolds L, Ganesh T, Dingledine R. Peripheral Myeloid Cell EP2 Activation Contributes to the Deleterious Consequences of Status Epilepticus. Journal Of Neuroscience 2020, 41: 1105-1117. PMID: 33293358, PMCID: PMC7880294, DOI: 10.1523/jneurosci.2040-20.2020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFlow CytometryHippocampusImmunity, InnateMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMyeloid CellsReceptors, Prostaglandin E, EP2 SubtypeStatus EpilepticusConceptsBlood-brain barrierImmune myeloid cellsEP2 receptorInnate immune cellsStatus epilepticusEP2 antagonismProstaglandin EP2 receptorBlood-borne monocytesMyeloid cellsImmune cellsConsequences of seizuresBrain infiltrationInflammatory cytokinesFormation of inflammatory cytokinesConditional KOInflammatory responsePeripheral innate immune cellsActivation of EP2 receptorsQuality of lifeEP2 receptor antagonistRecruitment of blood-borne monocytesSerum albumin levelPeripheral immune cellsConsequences of status epilepticusHippocampal IL-6
2018
Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
Sumida T, Lincoln MR, Ukeje CM, Rodriguez DM, Akazawa H, Noda T, Naito AT, Komuro I, Dominguez-Villar M, Hafler DA. Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity. Nature Immunology 2018, 19: 1391-1402. PMID: 30374130, PMCID: PMC6240373, DOI: 10.1038/s41590-018-0236-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmunitybeta CateninGene Expression RegulationHumansInflammationInterferon-gammaInterleukin-10Mice, Inbred C57BLMultiple Sclerosis, Relapsing-RemittingReceptors, Prostaglandin E, EP2 SubtypeT-Lymphocytes, RegulatoryConceptsProstaglandin E receptor 2Regulatory T cellsTreg cellsT cellsAnti-inflammatory cytokine productionIL-10 productionPeripheral immune toleranceIL-10 expressionΒ-cateninE receptor 2Treg subpopulationsTreg phenotypeIL-10Cytokines IFNImmune toleranceTreg signatureCytokine signatureMultiple sclerosisAutoimmune diseasesCytokine productionInflammatory environmentLethal autoimmunityReceptor 2Activated β-cateninIFN
2015
Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection
Chen JH, Perry CJ, Tsui YC, Staron MM, Parish IA, Dominguez CX, Rosenberg DW, Kaech SM. Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection. Nature Medicine 2015, 21: 327-334. PMID: 25799228, PMCID: PMC4505619, DOI: 10.1038/nm.3831.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBcl-2-Like Protein 11CelecoxibCell SurvivalDinoprostoneFemaleLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMembrane ProteinsMiceMice, Inbred C57BLMice, TransgenicProgrammed Cell Death 1 ReceptorProto-Oncogene ProteinsPyrazolesReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 SubtypeSignal TransductionSulfonamidesT-Lymphocytes, Cytotoxic
2014
Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells
Kofler DM, Marson A, Dominguez-Villar M, Xiao S, Kuchroo VK, Hafler DA. Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells. Journal Of Clinical Investigation 2014, 124: 2513-2522. PMID: 24812667, PMCID: PMC4089462, DOI: 10.1172/jci72973.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAutoimmunityCase-Control StudiesDinoprostoneDown-RegulationFemaleGene Knockdown TechniquesGene SilencingHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedModels, ImmunologicalMultiple SclerosisNuclear Receptor Subfamily 1, Group F, Member 3PhenotypePromoter Regions, GeneticReceptors, Prostaglandin E, EP2 SubtypeSignal TransductionTh17 CellsConceptsTh17 cell phenotypeProstaglandin receptor EP2Receptor EP2Healthy individualsOverexpression of EP2Transcription factor RORCT cell subsetsEffects of PGE2Cell phenotypeExpression of IFNInflammatory gene transcriptionPGE2-dependent pathwayTh17 cellsWT miceAutoimmune diseasesCell subsetsHealthy subjectsEP2 expressionGM-CSFEP2RORCCD4Cell typesCellsGene transcription
2012
Prostaglandin E2 Affects T Cell Responses through Modulation of CD46 Expression
Kickler K, Maltby K, Choileain S, Stephen J, Wright S, Hafler DA, Jabbour HN, Astier AL. Prostaglandin E2 Affects T Cell Responses through Modulation of CD46 Expression. The Journal Of Immunology 2012, 188: 5303-5310. PMID: 22544928, PMCID: PMC3758685, DOI: 10.4049/jimmunol.1103090.Peer-Reviewed Original ResearchConceptsG protein-coupled receptor kinasesCell functionProtein-coupled receptor kinasesT cell functionT cell activationG protein-coupled receptorsProtein-coupled receptorsCD46 expressionPrimary T cellsReceptor kinaseT cellsCD46 functionsCell activationRegulatory mechanismsDiverse rolesDifferentiation pathwayNovel roleCytokine productionProstanoid familyActivation signalsActivated T cellsT cell responsesChronic inflammatory diseaseSubtypes of receptorsCD46 activation
2010
Prostaglandin receptors EP2 and IP are detectable in atherosclerotic arteries and plaques.
Muto A, Nishibe T, Miyauchi Y, Kondo Y, Yamamoto Y, Dardik A, Shigematsu H. Prostaglandin receptors EP2 and IP are detectable in atherosclerotic arteries and plaques. International Angiology 2010, 29: 43-8. PMID: 20357748.Peer-Reviewed Original ResearchConceptsArteriosclerosis obliteransAtherosclerotic femoral arteriesPharmacological treatmentFemoral arteryReceptor EP2IP receptorAtherosclerotic plaquesMedial layerAtherosclerotic arteriesWestern blottingSevere arteriosclerosis obliteransFemoropopliteal bypass surgeryCOX-2 expressionProstaglandin receptor agonistsProstaglandin receptor EP2Pharmacological managementBypass surgeryReceptor agonistArterial intimaIntimal layerPG receptorsArteryPlatelet aggregationPatientsEP2PTGER2 Overexpression in Colorectal Cancer Is Associated with Microsatellite Instability, Independent of CpG Island Methylator Phenotype
Baba Y, Nosho K, Shima K, Goessling W, Chan AT, Ng K, Chan JA, Giovannucci EL, Fuchs CS, Ogino S. PTGER2 Overexpression in Colorectal Cancer Is Associated with Microsatellite Instability, Independent of CpG Island Methylator Phenotype. Cancer Epidemiology Biomarkers & Prevention 2010, 19: 822-831. PMID: 20200425, PMCID: PMC2837535, DOI: 10.1158/1055-9965.epi-09-1154.Peer-Reviewed Original ResearchMeSH Keywordsbeta CateninBiomarkers, TumorColorectal NeoplasmsCpG IslandsCyclooxygenase 2DNA MethylationFemaleHumansImmunohistochemistryKaplan-Meier EstimateMaleMicrosatellite InstabilityPhenotypePrognosisReceptors, Prostaglandin EReceptors, Prostaglandin E, EP2 SubtypeReverse Transcriptase Polymerase Chain ReactionTumor Suppressor Protein p53ConceptsCpG island methylator phenotypeColorectal cancerMicrosatellite instabilityEnzymatic product prostaglandin E2MSI-high colorectal cancerEight-marker panelMethylator phenotypeProspective cohort studyClinical outcome dataProduct prostaglandin E2Prostaglandin-endoperoxide synthase 2Signet ring cellsLINE-1 hypomethylationCohort studyMucinous componentPatient survivalPrognostic significanceInflammatory reactionProstaglandin E2Outcome dataColon cancerMultivariate analysisRing cellsCancerCTNNB1 expression
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