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
2018
Cenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents
Yu D, Cai S, Mennone A, Vig P, Boyer JL. Cenicriviroc, a cytokine receptor antagonist, potentiates all‐trans retinoic acid in reducing liver injury in cholestatic rodents. Liver International 2018, 38: 1128-1138. PMID: 29356312, PMCID: PMC6032984, DOI: 10.1111/liv.13698.Peer-Reviewed Original ResearchConceptsBile acid pool sizeTrans retinoic acidAcid pool sizePlasma liver enzymesLiver injurySuperior therapeutic effectLiver necrosisLiver enzymesT cellsTherapeutic effectRetinoic acidAntagonist of CCR2Hepatic inflammatory cellsCholestatic liver injuryBile duct proliferationBody weight ratioCholestatic liver diseasePro-inflammatory cytokinesCytokine receptor antagonistsHepatic hydroxyproline contentExpression of cytokinesDuct-ligated ratsBile acid synthesisHepatic infiltrationLiver disease
2017
Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areas
2015
Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury
Li M, Mennone A, Soroka CJ, Hagey LR, Ouyang X, Weinman EJ, Boyer JL. Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury. Hepatology 2015, 62: 1227-1236. PMID: 26108984, PMCID: PMC4589453, DOI: 10.1002/hep.27956.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver injuryInflammatory responseICAM-1BDL miceBDL-induced liver injuryNeutrophil-mediated liver injuryTotal bile acid concentrationTumor necrosis factor alphaIntercellular adhesion molecule-1Hepatic neutrophil accumulationAttenuated liver injuryCholestatic liver injuryHepatic inflammatory responseMouse liverSerum alanine aminotransferaseBile acid concentrationsHepatic inflammatory diseasesICAM-1 expressionNecrosis factor alphaAdhesion molecule-1Wild-type miceICAM-1 proteinNew therapeutic targetsMessenger RNA levels
2010
The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease
Lam P, Soroka C, Boyer J. The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease. Seminars In Liver Disease 2010, 30: 125-133. PMID: 20422495, PMCID: PMC3008346, DOI: 10.1055/s-0030-1253222.Peer-Reviewed Original ResearchConceptsBenign recurrent intrahepatic cholestasis type 2Progressive familial intrahepatic cholestasis type 2Bile salt export pumpDrug-induced cholestasisType 2Export pumpCholestatic liver diseaseBile salt secretionForms of cholestasisDifferent genetic formsLiver diseaseCholestatic disordersIntrahepatic cholestasisBSEP expressionPathophysiologic processesBSEP deficiencyAnimal modelsCholestasisGenetic formsBile saltsSalt secretionMolecular characteristicsPivotal roleCell culturesPrimary transporter
2001
Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes
Mennone A, Biemesderfer D, Negoianu D, Yang C, Abbiati T, Schultheis P, Shull G, Aronson P, Boyer J. Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. AJP Gastrointestinal And Liver Physiology 2001, 280: g247-g254. PMID: 11208547, DOI: 10.1152/ajpgi.2001.280.2.g247.Peer-Reviewed Original Research