2023
Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis
Mooring M, Yeung G, Luukkonen P, Liu S, Akbar M, Zhang G, Balogun O, Yu X, Mo R, Nejak-Bowen K, Poyurovsky M, Booth C, Konnikova L, Shulman G, Yimlamai D. Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis. Science Translational Medicine 2023, 15: eade3157. PMID: 37756381, PMCID: PMC10874639, DOI: 10.1126/scitranslmed.ade3157.Peer-Reviewed Original ResearchConceptsNonalcoholic steatohepatitisLiver inflammationNonalcoholic fatty liver diseaseProgression of NASHCysteine-rich angiogenic inducer 61Fatty liver diseaseLiver-specific knockout miceImproved glucose toleranceType 2 diabetesGlucose toleranceLiver diseaseNASH progressionProfibrotic macrophagesProinflammatory propertiesReduced fibrosisCardiovascular diseaseProfibrotic phenotypeFibrotic developmentKnockout miceNF-κBMetabolic diseasesNASH dietPDGFB expressionFibrosisProfibrotic program
2020
The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source
Wen L, Javed TA, Dobbs AK, Brown R, Niu M, Li L, Khalid A, Barakat M, Xiao X, Yimlamai D, Konnikova L, Yu M, Byersdorfer CA, Husain SZ. The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source. Gastroenterology 2020, 159: 1036-1050.e8. PMID: 32445858, PMCID: PMC7502475, DOI: 10.1053/j.gastro.2020.05.051.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAcute Lung InjuryAnimalsBone Marrow CellsCalcineurinCalcineurin InhibitorsCalcium-Binding ProteinsCells, CulturedCeruletideCytokinesDisease Models, AnimalFemaleHumansMaleMiceMice, TransgenicMuscle ProteinsNeutrophilsNFATC Transcription FactorsPancreasPancreatitisPrimary Cell CultureConceptsAdministration of caeruleinLocal pancreatic inflammationBiliopancreatic ductPancreas-specific deletionLung inflammationPancreatic inflammationAcute pancreatitisControl miceNeutrophil chemotaxisProtective effectHematopoietic-specific deletionPancreatic acinar cell necrosisPrevention of pancreatitisLevels of cytokinesAcinar cell necrosisSwiss Webster miceActivated T cellsAdeno-associated virus vectorPrimary pancreatic acinar cellsReactive oxygen species productionNFAT-luciferaseSevere pancreatitisCalcineurin inhibitorsNeutrophil expressionPancreatic acinar cells
2019
Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model
Goettel JA, Kotlarz D, Emani R, Canavan JB, Konnikova L, Illig D, Frei SM, Field M, Kowalik M, Peng K, Gringauz J, Mitsialis V, Wall SM, Tsou A, Griffith AE, Huang Y, Friedman JR, Towne JE, Plevy SE, Hall A, Snapper SB. Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model. Cellular And Molecular Gastroenterology And Hepatology 2019, 8: 193-195. PMID: 31078723, PMCID: PMC6661391, DOI: 10.1016/j.jcmgh.2019.05.001.Peer-Reviewed Original Research
2016
Interleukin 1β Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency
Shouval DS, Biswas A, Kang YH, Griffith AE, Konnikova L, Mascanfroni ID, Redhu NS, Frei SM, Field M, Doty AL, Goldsmith JD, Bhan AK, Loizides A, Weiss B, Yerushalmi B, Yanagi T, Lui X, Quintana FJ, Muise AM, Klein C, Horwitz BH, Glover SC, Bousvaros A, Snapper SB. Interleukin 1β Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency. Gastroenterology 2016, 151: 1100-1104. PMID: 27693323, PMCID: PMC5124405, DOI: 10.1053/j.gastro.2016.08.055.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdultAnimalsAntirheumatic AgentsCaspase 8CD4-Positive T-LymphocytesCells, CulturedChild, PreschoolColitisGene Expression RegulationHomeodomain ProteinsHumansImmunity, InnateInflammasomesInflammatory Bowel DiseasesInterferon-gammaInterleukin 1 Receptor Antagonist ProteinInterleukin-10Interleukin-10 Receptor alpha SubunitInterleukin-17Interleukin-1betaLipopolysaccharidesMacrophagesMiceMice, KnockoutMutationNLR Family, Pyrin Domain-Containing 3 ProteinProtein BiosynthesisReceptors, Interleukin-10Signal TransductionTumor Necrosis Factor-alphaConceptsInflammatory bowel diseaseProduction of IL1βBowel diseaseIntestinal inflammationT cellsAllogeneic hematopoietic stem cell transplantationInterleukin-10 Receptor DeficiencyHematopoietic stem cell transplantationStem cell transplantationInnate immune cellsActivation of CD4IL1 receptor antagonistTumor necrosis factorInterleukin-10 receptorProduction of IL1Stimulation of macrophagesImmune productionSpontaneous colitisReceptor deficiencyCell transplantationHistologic responseImmune cellsInterleukin-1βDeficient miceNecrosis factor