2024
Inflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation
Taru V, Szabo G, Mehal W, Reiberger T. Inflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation. Journal Of Hepatology 2024, 81: 895-910. PMID: 38908436, DOI: 10.1016/j.jhep.2024.06.016.Peer-Reviewed Original ResearchAcute-on-chronic liver failureChronic liver diseaseLiver disease progressionToll-like receptorsLiver diseasePortal hypertensionLiver failureDisease progressionLiver injuryImmune systemEnd-stage liver diseaseRelease of pro-inflammatory cytokinesInnate immune cellsFlares of inflammationDysfunctional immune systemInflammasome activationPro-inflammatory stateNuclear factor kappa BPro-inflammatory cytokinesAdaptive immune systemFactor kappa BSystemic inflammationLiver parenchymal cellsWhite adipose tissueImmune cellsComplement protein signatures in patients with alcohol-associated hepatitis
Taiwo M, Huang E, Pathak V, Bellar A, Welch N, Dasarathy J, Streem D, McClain C, Mitchell M, Barton B, Szabo G, Dasarathy S, Consortium A, Schaefer E, Luther J, Day L, Ouyang X, Suyavaran A, Mehal W, Jacobs J, Goodman R, Rotroff D, Nagy L. Complement protein signatures in patients with alcohol-associated hepatitis. JCI Insight 2024, 9: e174127. PMID: 38573776, PMCID: PMC11141929, DOI: 10.1172/jci.insight.174127.Peer-Reviewed Original ResearchAlcohol-associated hepatitisSevere AHAlcohol use disorderAlcoholic cirrhosisHealthy controlsPredicting 90-day mortalityComplement proteinsSerum proteome of patientsEthanol-induced liver injurySerum proteomeDevelopment of effective therapiesProteome of patientsAssociated with pro-inflammatory cytokinesProtein signaturesPro-inflammatory cytokinesCoagulation factors IINon-invasive biomarkersDiagnostic challengeSerine protease 1Murine modelEffective therapyLiver injuryPrognostic biomarkerHepatic inflammationC1q binding protein
2014
Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity
Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity. Gastroenterology 2014, 146: 1763-1774. PMID: 24657625, PMCID: PMC4104305, DOI: 10.1053/j.gastro.2014.03.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCell LineCeruletideChemical and Drug Induced Liver InjuryCytoprotectionDisease Models, AnimalDose-Response Relationship, DrugDown-RegulationGalactosamineHumansImmunity, InnateInflammasomesInjections, IntraperitonealInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLMonocytesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisReceptors, G-Protein-CoupledRNA InterferenceRNA, Small InterferingSignal TransductionSodium LactateToll-Like Receptor 4Toll-Like ReceptorsTransfectionConceptsToll-like receptorsRelease of IL1βAdministration of lipopolysaccharideOrgan injuryNF-κBCaspase-1TLR inductionAcute pancreatitisPyrin domain-containing protein 3Administration of lactatePromising immunomodulatory therapyAcute liver injuryAcute organ injuryMacrophages of miceDomain-containing protein 3Production of IL1βRAW 264.7 cellsConcentration of lactateAcute hepatitisImmunomodulatory therapyImmune hepatitisPancreatic injuryLactate receptorLiver injuryNLRP3 inflammasome
2013
The Immunopathogenesis of Cirrhosis
Gao B, Friedman S, Mehal W. The Immunopathogenesis of Cirrhosis. 2013, 413-424. DOI: 10.1007/978-3-319-02096-9_28.Peer-Reviewed Original ResearchHepatocellular carcinomaProgressive liver injuryChronic liver diseaseNatural killer cellsImmune cell subsetsAltered hepatic functionInnate immune responseWound healing responseViral hepatitisLiver injuryFibrosis progressionKiller cellsLiver diseaseAutoimmune diseasesCell subsetsChronic injuryHepatic fibrosisFibrogenic responseFibrosis resolutionHepatic functionHepatic parenchymaVascular remodelingImmune responseHepatocellular apoptosisBlood flow
2012
Sterile Inflammation in the Liver
Kubes P, Mehal WZ. Sterile Inflammation in the Liver. Gastroenterology 2012, 143: 1158-1172. PMID: 22982943, DOI: 10.1053/j.gastro.2012.09.008.Peer-Reviewed Original ResearchMeSH KeywordsAcetaminophenAdenosine TriphosphateCaspase 1Chemical and Drug Induced Liver InjuryChemotaxis, LeukocyteCytokinesFatty LiverFatty Liver, AlcoholicHepatitisHMGB1 ProteinHumansInflammasomesInterleukin-1betaNeutrophilsNon-alcoholic Fatty Liver DiseaseNucleic AcidsReceptors, Pattern RecognitionReperfusion InjurySignal TransductionUric AcidConceptsDamage-associated molecular patternsPattern recognition receptorsImmune cellsSterile inflammationRecognition receptorsCellular pattern recognition receptorsDrug-induced liver injuryEndogenous damage-associated molecular patternsSuch damage-associated molecular patternsMolecular patternsSite of injuryPathogen-associated molecular patternsProtease caspase-1Alcoholic steatohepatitisLiver injuryNonalcoholic steatohepatitisLiver diseaseProinflammatory cytokinesSpecific therapyInterleukin-1βLiver pathologyTissue injuryImmune responseTherapeutic targetActivate receptors
2010
Cell Death and Fibrogenesis
Mehal W, Imaeda A. Cell Death and Fibrogenesis. Seminars In Liver Disease 2010, 30: 226-231. PMID: 20665375, PMCID: PMC3219753, DOI: 10.1055/s-0030-1255352.BooksConceptsHepatic stellate cellsQuiescent hepatic stellate cellsChronic liver injuryNatural killer cellsCell deathHIV infectionLiver injuryNK cellsKiller cellsAntifibrotic effectsImmune suppressionImmune cellsProfibrotic effectsStellate cellsHepatocyte deathHSC apoptosisDeathCellular deathFibrosisCellular debrisMatrix depositionHSC deathSurvival signalsApoptotic bodiesProapoptotic signals
2009
Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome
Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, Flavell RA, Mehal WZ. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. Journal Of Clinical Investigation 2009, 119: 305-314. PMID: 19164858, PMCID: PMC2631294, DOI: 10.1172/jci35958.Peer-Reviewed Original ResearchMeSH KeywordsAcetaminophenAnalgesics, Non-NarcoticAnimalsApoptosisAspirinCarrier ProteinsCaspase InhibitorsCell LineCyclooxygenase InhibitorsDose-Response Relationship, DrugHumansImmunity, InnateInflammationInterleukin-18Interleukin-1betaLiverMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinSignal TransductionToll-Like Receptor 9ConceptsLiver injuryIL-1betaNALP3 inflammasomeHepatocyte deathAcetaminophen-induced liver injuryCaspase-1Proinflammatory cytokine activationInnate immune activationSterile inflammatory responseType of injuryCOX-1 inhibitionMature IL-1betaPotential therapeutic approachSinusoidal endothelial cellsOverall tissue injuryIL-18Immune activationProinflammatory cytokinesTLR9 antagonistInitial insultInflammatory responseTissue injuryProtective effectCytokine activationTherapeutic approaches
2001
Antigen Presentation by Liver Cells Controls Intrahepatic T Cell Trapping, Whereas Bone Marrow-Derived Cells Preferentially Promote Intrahepatic T Cell Apoptosis
Mehal W, Azzaroli F, Crispe I. Antigen Presentation by Liver Cells Controls Intrahepatic T Cell Trapping, Whereas Bone Marrow-Derived Cells Preferentially Promote Intrahepatic T Cell Apoptosis. The Journal Of Immunology 2001, 167: 667-673. PMID: 11441069, DOI: 10.4049/jimmunol.167.2.667.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationApoptosisBone Marrow CellsBone Marrow TransplantationCD8-Positive T-LymphocytesCell MovementCells, CulturedCytotoxicity, ImmunologicLiverLymphocyte ActivationLymphocyte CountLymphocyte DepletionMiceMice, Inbred C57BLMice, TransgenicRadiation ChimeraSpleenStem Cell TransplantationStem CellsConceptsMarrow-derived cellsNon-bone marrow-derived cellsT cellsT cell apoptosisAg presentationLiver injuryBone marrow-derived cellsCell apoptosisSuch liver injuryT cell trappingT cell accumulationBone marrow chimerasTCR transgenic miceT cell populationsT cell deletionAdoptive transferIntrahepatic accumulationLiver damageHepatocyte damageSystemic activationAntigen presentationBone marrowCell accumulationClonal expansionCell deletion