2020
Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis
Cai SY, Yu D, Soroka CJ, Wang J, Boyer JL. Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis. Journal Of Hepatology 2020, 74: 550-559. PMID: 33039404, PMCID: PMC7897288, DOI: 10.1016/j.jhep.2020.09.035.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter, Subfamily BBile Acids and SaltsCells, CulturedCholangitis, SclerosingCytokinesDisease Models, AnimalFemaleGene Expression RegulationGene Knockdown TechniquesHepatocytesHumansLiverLiver Cirrhosis, BiliaryMiceMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsPyrazolesSignal TransductionTreatment OutcomeConceptsCholestatic liver injuryLiver injuryInflammatory genesIL-8NFAT activationCholestatic liver tissuesHepatic cytokine expressionReduced liver injurySpecific NFAT inhibitorsHepatic inflammatory responseInduces liver injuryMouse hepatocytesIL-8 expressionActivated T cellsIL-8 promoterElevated tissue levelsGene reporterInflammatory cytokinesCytokine expressionElevated mRNA levelsInflammatory responseCholestatic liverT cellsImmune responseNFAT inhibitor
2019
Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse
Cai SY, Ge M, Mennone A, Hoque R, Ouyang X, Boyer JL. Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse. Cellular And Molecular Gastroenterology And Hepatology 2019, 9: 679-688. PMID: 31887435, PMCID: PMC7160576, DOI: 10.1016/j.jcmgh.2019.12.008.Peer-Reviewed Original ResearchConceptsWT BDL miceCholestatic liver injuryBDL liversBDL miceBile duct ligationBile acidsLiver injuryCholestatic patientsIL-1βM2 anti-inflammatory macrophagesPrimary sclerosing cholangitisPlasma IL-1βLiver hydroxyproline contentLiver of patientsPrimary biliary cholangitisHealthy control subjectsCD206-positive cellsAnti-inflammatory macrophagesIL-1β inductionEndogenous bile acidsCaspase-1 cleavageProcaspase-1 cleavageMouse hepatocytesSclerosing cholangitisLiver histology
2016
CFTR-associated ligand is a negative regulator of Mrp2 expression
Li M, Soroka CJ, Harry K, Boyer JL. CFTR-associated ligand is a negative regulator of Mrp2 expression. American Journal Of Physiology - Cell Physiology 2016, 312: c40-c46. PMID: 27834195, PMCID: PMC5283898, DOI: 10.1152/ajpcell.00100.2016.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCells, CulturedChlorocebus aethiopsCOS CellsDown-RegulationGene Expression RegulationGolgi Matrix ProteinsHepatocytesHumansMaleMembrane ProteinsMembrane Transport ProteinsMiceMultidrug Resistance-Associated Protein 2Multidrug Resistance-Associated ProteinsRatsRats, Sprague-DawleySignal TransductionConceptsPull-down assaysGST pull-down assaysCOOH-terminal PDZNegative regulatorCotransfected COS-7 cellsGlutathione S-transferase fusion proteinS-transferase fusion proteinATP-binding cassette (ABC) transportersTrans-Golgi networkCystic fibrosis transmembrane conductance regulatorProtein-protein interactionsExchanger regulatory factor 1Fibrosis transmembrane conductance regulatorStreptavidin pull-down assaysTransmembrane conductance regulatorCOS-7 cellsRegulatory factor 1PDZ domainCell surface expressionPosttranscriptional regulationTransmembrane proteinPlasma membraneLLC-PK1 cellsCassette transportersCOS-7
2010
Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells
He H, Mennone A, Boyer JL, Cai S. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct–ligated rats and human hepatic cells. Hepatology 2010, 53: 548-557. PMID: 21274875, PMCID: PMC3069505, DOI: 10.1002/hep.24047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsBile DuctsCell ProliferationCells, CulturedCholestasis, IntrahepaticCholesterol 7-alpha-HydroxylaseCollagen Type ICollagen Type I, alpha 1 ChainDisease Models, AnimalHepatocytesHumansLigationLiverMaleMatrix Metalloproteinase 2RatsRats, Sprague-DawleySmad2 ProteinTretinoinUrsodeoxycholic AcidConceptsBile duct ligationBile salt pool sizeLX-2 cellsUrsodeoxycholic acidHepatic stellate cellsRetinoic acidLiver fibrosisStellate cellsPhosphate-buffered salineCommon bile duct ligationMale Sprague-Dawley ratsPrimary human hepatic stellate cellsTumor necrosis factor αBile duct-ligated ratsHuman hepatic stellate cellsBile duct proliferationHuman hepatocytesLiver hydroxyproline contentNecrosis factor αSprague-Dawley ratsAcute promyelocytic leukemiaΑ-SMA expressionDuct-ligated ratsSmooth muscle actinMatrix metalloproteinase-2
2001
Cl−-dependent secretory mechanisms in isolated rat bile duct epithelial units
Singh S, Mennone A, Gigliozzi A, Fraioli F, Boyer J. Cl−-dependent secretory mechanisms in isolated rat bile duct epithelial units. AJP Gastrointestinal And Liver Physiology 2001, 281: g438-g446. PMID: 11447024, DOI: 10.1152/ajpgi.2001.281.2.g438.Peer-Reviewed Original ResearchMeSH KeywordsAmmonium ChlorideAnimalsBariumBicarbonatesBile Ducts, IntrahepaticBumetanideCarbon DioxideCarrier ProteinsCell PolarityCells, CulturedChloridesColforsinEpithelial CellsHydrogen-Ion ConcentrationIon TransportMaleModels, BiologicalRatsRats, Sprague-DawleySodiumSodium-Potassium-Chloride SymportersConceptsCO2/HCOFluid secretionCotransport activityIntrahepatic bile duct epitheliumBile duct epitheliumDependent fluid secretionHigh intracellular Cl(-) concentrationIntracellular Cl- concentrationBile duct unitsApical Cl(-) secretionNH entryInitial acidification rateIntracellular cAMP concentrationNH4Cl exposureDuct epitheliumInhibitor bumetanideChannel inhibitorsCl(-) secretionCanalicular bileDuct unitsSecretionDependent secretionSecretory mechanismBumetanideForskolin
1999
Hepatic Toxicity and Persistence of ser/thr Protein Phosphatase Inhibition by Microcystin in the Little Skate Raja erinacea
Runnegar M, Seward D, Ballatori N, Crawford J, Boyer J. Hepatic Toxicity and Persistence of ser/thr Protein Phosphatase Inhibition by Microcystin in the Little Skate Raja erinacea. Toxicology And Applied Pharmacology 1999, 161: 40-49. PMID: 10558922, DOI: 10.1006/taap.1999.8783.Peer-Reviewed Original ResearchConceptsDose-dependent inhibitionSkate hepatocytesUptake of microcystinNear complete inhibitionPP activityInflammatory changesHepatic toxicityHepatocyte necrosisHistological changesAccompanying inhibitionHepatic lesionsBile acidsHigh dosesOnly organSignificant inhibitionSkate Raja erinaceaLittle skate Raja erinaceaInhibitionLiverRectal glandCanalicular Export Pumps Traffic with Polymeric Immunoglobulin A Receptor on the Same Microtubule-associated Vesicle in Rat Liver*
Soroka C, Pate M, Boyer J. Canalicular Export Pumps Traffic with Polymeric Immunoglobulin A Receptor on the Same Microtubule-associated Vesicle in Rat Liver*. Journal Of Biological Chemistry 1999, 274: 26416-26424. PMID: 10473600, DOI: 10.1074/jbc.274.37.26416.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile CanaliculiBiological TransportBiopolymersCells, CulturedLiverMicroscopy, ElectronMicrotubulesRatsReceptors, FcConceptsApical membrane proteinsMembrane proteinsMicrotubule-associated vesiclesSite of functionMembrane transport proteinsMembrane-bound vesiclesNon-hydrolyzable nucleotidesReceptor trafficMicrotubule motorsTransport proteinsIntermediate chainEssential pathwayPolymeric immunoglobulinsSame vesiclesTranscytotic vesiclesMultidrug resistance protein 2Protein 2Immunoelectron microscopyVesiclesMicrotubulesProteinVesicular transcytosisPathwayRat hepatocytesCanalicular export
1998
Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors.
Trauner M, Arrese M, Lee H, Boyer J, Karpen S. Endotoxin downregulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors. Journal Of Clinical Investigation 1998, 101: 2092-2100. PMID: 9593765, PMCID: PMC508797, DOI: 10.1172/jci1680.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Acids and SaltsCarrier ProteinsCells, CulturedCholestasisDNA-Binding ProteinsDown-RegulationEndotoxinsGene Expression RegulationHepatocyte Nuclear Factor 1Hepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaLiverMaleMembrane Transport ProteinsNuclear ProteinsOrganic Anion Transporters, Sodium-DependentPromoter Regions, GeneticRatsRats, Sprague-DawleyRNA, MessengerSepsisSymportersTranscription FactorsConceptsNuclear binding activityNtcp mRNA levelsMRNA levelsHepatobiliary transportersMRNA expressionCritical transcription factorTime pointsSepsis-associated cholestasisNuclear factor-kappaBSodium-dependent uptakeEffector cytokinesSequential time pointsEndotoxin administrationPretreatment levelsBinding activityMaximal decreaseBile acidsFactor-kappaBHepatocyte nuclear factor 1Normal levelsHepatic basolateral membraneNuclear factorMarked reductionCoordinated downregulationEndotoxin
1997
Enterohepatic circulation of scymnol sulfate in an elasmobranch, the little skate (Raja erinacea)
Fricker G, Wössner R, Drewe J, Fricker R, Boyer J. Enterohepatic circulation of scymnol sulfate in an elasmobranch, the little skate (Raja erinacea). American Journal Of Physiology 1997, 273: g1023-g1030. PMID: 9374698, DOI: 10.1152/ajpgi.1997.273.5.g1023.Peer-Reviewed Original ResearchConceptsEnterohepatic circulationScymnol sulfateBile alcohol sulfatesBile flowBiliary secretionCholeretic effectMajor bile saltsHepatic uptakeHepatic eliminationIntestinal epitheliumBileLiverSkate liverHepatic transportSpecific transport mechanismsBile alcoholsMajor metaboliteFirst direct demonstrationBile saltsCholyltaurinePerfusateLittle skatePolar metabolitesCompetitive mannerDirect demonstration
1996
Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes
Beuers U, Throckmorton D, Anderson, Isales C, Thasler W, Kullak-Ublick G, Sauter G, Koebe H, Paumgartner G, Boyer J. Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes. Gastroenterology 1996, 110: 1553-1563. PMID: 8613063, DOI: 10.1053/gast.1996.v110.pm8613063.Peer-Reviewed Original ResearchConceptsEffect of TUDCATauroursodeoxycholic acidProtein kinase CHepatocellular Ca2Chronic cholestatic liver diseaseCholestatic liver diseaseAlpha-PKCPKC activityLiver diseaseLiver functionRadioenzymatic techniqueExperimental cholestasisPhorbol ester phorbolActivation of PKCKinase CTaurocholic acidImmunofluorescence techniqueAbstractTextMembrane-associated PKC activitySignificant increaseAIMSStimulation of exocytosisUnknown mechanismParticulate membrane fractionHepatocytes
1995
Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets
Boyer J, Soroka C. Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets. Gastroenterology 1995, 109: 1600-1611. PMID: 7557144, DOI: 10.1016/0016-5085(95)90649-5.Peer-Reviewed Original ResearchConceptsInsertion of vesiclesTranslocation of vesiclesMembrane transport activityVesicle trafficApical domainIsolated rat hepatocyte coupletsAcid transportersTransport activityNocodazoleRat hepatocyte coupletsVesiclesIndependent mechanismsEpithelial cellsBile acid transporterSite of residenceHepatocyte coupletsTransportersCanalicular membraneRat hepatocytesImmunocytochemical localizationCyclic monophosphateAdenosine triphosphataseBile excretory functionATP depletion and inactivation of an ATP-sensitive taurine channel by classic ion channel blockers.
Ballatori N, Truong A, Jackson P, Strange K, Boyer J. ATP depletion and inactivation of an ATP-sensitive taurine channel by classic ion channel blockers. Molecular Pharmacology 1995, 48: 472-6. PMID: 7565627.Peer-Reviewed Original ResearchConceptsIon channel blockersChannel blockersVolume-activated anion channelsATP levelsATP contentActivity of ATPPhysiologic alterationsIntracellular ATP levelsCellular ATPTaurine effluxBlockersIntracellular ATP contentTaurine channelCellular ATP levelsATP/ADP ratioIntracellular organic osmolytesSkate hepatocytesIntracellular ATPATP depletionCell volume regulationDifferent cell typesEffluxCellular ATP concentrationMetabolic poisonsCell types
1993
Characterization of bumetanide transport in isolated skate hepatocytes
Blumrich M, Petzinger E, Boyer J. Characterization of bumetanide transport in isolated skate hepatocytes. American Journal Of Physiology 1993, 265: g926-g933. PMID: 8238522, DOI: 10.1152/ajpgi.1993.265.5.g926.Peer-Reviewed Original Research
1992
Taurine transport in skate hepatocytes. I. Uptake and efflux
Ballatori N, Boyer J. Taurine transport in skate hepatocytes. I. Uptake and efflux. American Journal Of Physiology 1992, 262: g445-g450. PMID: 1550234, DOI: 10.1152/ajpgi.1992.262.3.g445.Peer-Reviewed Original ResearchConceptsSkate hepatocytesDependent uptake processIntracellular taurine levelsTaurine uptake systemsTaurine levelsMicroM taurineTaurine uptakeIsosmotic replacementTaurine transportEfflux pathwaySlow effluxExtracellular ClIndependent uptake systemAmino sulfonic acidI. UptakeTaurine accumulationHepatocytesUptake systemEffluxTaurineDisulfonic acidBeta-amino acidsDistinct mechanismsUptakeReplacementTaurine transport in skate hepatocytes. II. Volume activation, energy, and sulfhydryl dependence
Ballatori N, Boyer J. Taurine transport in skate hepatocytes. II. Volume activation, energy, and sulfhydryl dependence. American Journal Of Physiology 1992, 262: g451-g460. PMID: 1550235, DOI: 10.1152/ajpgi.1992.262.3.g451.Peer-Reviewed Original Research
1991
Cl(-)-HCO3- exchanger in isolated rat hepatocytes: role in regulation of intracellular pH
Benedetti A, Strazzabosco M, Corasanti J, Haddad P, Graf J, Boyer J. Cl(-)-HCO3- exchanger in isolated rat hepatocytes: role in regulation of intracellular pH. American Journal Of Physiology 1991, 261: g512-g522. PMID: 1887897, DOI: 10.1152/ajpgi.1991.261.3.g512.Peer-Reviewed Original ResearchMeSH Keywords4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAmmoniaAnimalsBariumBicarbonatesCarrier ProteinsCells, CulturedChloride-Bicarbonate AntiportersChloridesHydrogen-Ion ConcentrationIntracellular FluidKineticsLiverMaleRatsRats, Inbred StrainsConceptsAlkaline loadPH-sensitive dye BCECFMM H2DIDSPHi recoveryRegulation of intracellularRat hepatocyte monolayersAcid extrudersMM DIDSRat hepatocytesElectrophysiological techniquesDye BCECFHCO3- exchangerIsolated rat hepatocytesConstant pHoIntracellularMembrane potentialHepatocyte monolayersHepatocytesAcid loadingEffect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers
Strazzabosco M, Sakisaka S, Hayakawa T, Boyer J. Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers. American Journal Of Physiology 1991, 260: g58-g69. PMID: 1987808, DOI: 10.1152/ajpgi.1991.260.1.g58.Peer-Reviewed Original ResearchConceptsBiliary HCO3- concentrationUrsodeoxycholic acidRat hepatocyte coupletsBiliary pHAcid loadEffect of UDCABile duct lumenHepatocyte coupletsIsolated rat hepatocyte coupletsBiliary epitheliumHCO3- concentrationDuct lumenRemoval of ClHCO3- exchangeRat liverLiverIPRLHepatocytesHypercholeresisPerfusateBileExcretionEpitheliumAmiloride
1990
DBcAMP stimulates vesicle transport and HRP excretion in isolated perfused rat liver
Hayakawa T, Bruck R, Ng O, Boyer J. DBcAMP stimulates vesicle transport and HRP excretion in isolated perfused rat liver. American Journal Of Physiology 1990, 259: g727-g735. PMID: 2173414, DOI: 10.1152/ajpgi.1990.259.5.g727.Peer-Reviewed Original ResearchConceptsBiliary excretionBile acidsBile acid excretionLiver 1Effects of adenosineRat liverElectron microscopic morphometric analysisTranscytotic vesicle pathwayLate peakHRP excretionHorseradish peroxidaseMin infusionBile flowExcretory functionAcid excretionO-dibutyryl cAMPPrimary hepatocyte culturesExcretionLiverDbcAMPCyclic monophosphateInfusionPericanalicular areaEffects of osmotic stresses on isolated rat hepatocytes. I. Ionic mechanisms of cell volume regulation
Corasanti J, Gleeson D, Boyer J. Effects of osmotic stresses on isolated rat hepatocytes. I. Ionic mechanisms of cell volume regulation. American Journal Of Physiology 1990, 258: g290-g298. PMID: 2305895, DOI: 10.1152/ajpgi.1990.258.2.g290.Peer-Reviewed Original ResearchMeSH Keywords4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAmilorideAnimalsBariumBicarbonatesBumetanideCells, CulturedChloridesHypertonic SolutionsHypotonic SolutionsKineticsLiverMaleOsmolar ConcentrationPotassium ChlorideQuinineRatsRats, Inbred StrainsSodium ChlorideEffects of osmotic stresses on isolated rat hepatocytes. II. Modulation of intracellular pH
Gleeson D, Corasanti J, Boyer J. Effects of osmotic stresses on isolated rat hepatocytes. II. Modulation of intracellular pH. American Journal Of Physiology 1990, 258: g299-g307. PMID: 2305896, DOI: 10.1152/ajpgi.1990.258.2.g299.Peer-Reviewed Original ResearchMeSH Keywords4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnimalsBicarbonatesBuffersCells, CulturedCholineHydrogen-Ion ConcentrationHypertonic SolutionsHypotonic SolutionsIntracellular FluidKineticsLiverMaleOsmolar ConcentrationRatsRats, Inbred StrainsSodiumConceptsRegulatory volume decreaseAbsence of HCO3Presence of HCO3Acid-base transport systemsModulation of intracellularRat hepatocytesVolume regulationAcute withdrawalMM amilorideGreater intracellularHCO3- exchangeAcid effluxIsotonic mediumIsolated rat hepatocytesSame maneuverCell volume regulationHepatocytesNet acid effluxAmilorideSubconfluent monolayersDisulfonic acidIntracellularVolume decreaseHypotonic mediumHypertonic medium