Role of caspase-1 and interleukin-1beta in acetaminophen-induced hepatic inflammation and liver injury.

Toxicology and Applied Pharmacology
C David WilliamsHartmut Jaeschke

Abstract

Acetaminophen (APAP) overdose can result in serious liver injury and potentially death. Toxicity is dependent on metabolism of APAP to a reactive metabolite initiating a cascade of intracellular events resulting in hepatocellular necrosis. This early injury triggers a sterile inflammatory response with formation of cytokines and innate immune cell infiltration in the liver. Recently, IL-1beta signaling has been implicated in the potentiation of APAP-induced liver injury. To test if IL-1beta formation through caspase-1 is critical for the pathophysiology, C57Bl/6 mice were treated with the pan-caspase inhibitor Z-VD-fmk to block the inflammasome-mediated maturation of IL-1beta during APAP overdose (300 mg/kg APAP). This intervention did not affect IL-1beta gene transcription but prevented the increase in IL-1beta plasma levels. However, APAP-induced liver injury and neutrophil infiltration were not affected. Similarly, liver injury and the hepatic neutrophilic inflammation were not attenuated in IL-1-receptor-1 deficient mice compared to wild-type animals. To evaluate the potential of IL-1beta to increase injury, mice were given pharmacological doses of IL-1beta after APAP overdose. Despite increased systemic activation of neutr...Continue Reading

Citations

Mar 19, 2014·Cellular & Molecular Immunology·Ruonan XuFu-Sheng Wang
Jan 21, 2014·Toxicology and Applied Pharmacology·C David WilliamsHartmut Jaeschke
Jul 4, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Mariel R B BettoMaria M Campos
Mar 31, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ana-Cristina DragomirDebra L Laskin
Sep 19, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yuchao XieHartmut Jaeschke
Oct 1, 2013·Journal of Autoimmunity·Jorge Henao-MejiaRichard A Flavell
Dec 10, 2015·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Charalampos KatselisApostolos Papalois
Jul 31, 2014·Expert Review of Clinical Pharmacology·Gisa TiegsPetra Arck
Jan 5, 2016·Biological & Pharmaceutical Bulletin·Syu-ichi KannoShin Yomogida
Nov 30, 2015·Archives of Toxicology·Ahmed Ghallab
May 13, 2015·Pathology Oncology Research : POR·Tamás LőrinczAndrás Szarka
Jun 10, 2015·Nature Reviews. Gastroenterology & Hepatology·Gyongyi Szabo, Jan Petrasek
Apr 14, 2015·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Kuo DuHartmut Jaeschke
Aug 30, 2014·Toxicology and Applied Pharmacology·Yonas GetachewDwain L Thiele
Dec 4, 2016·Journal of Hepatology·Benjamin L Woolbright, Hartmut Jaeschke
Nov 5, 2017·Biochemical Society Transactions·Bernd Gesslbauer, Valery Bochkov
Jun 16, 2017·Gene Regulation and Systems Biology·Lisl Km ShodaBrett A Howell
Mar 18, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hartmut Jaeschke, Kuo Du
May 28, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Matthew McMillinSharon DeMorrow
Feb 14, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·André G OliveiraGustavo B Menezes
Jul 24, 2013·Journal of Gastroenterology and Hepatology·Rafaz HoqueWajahat Z Mehal
May 7, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Changchun CaiBrian S Zuckerbraun
Aug 5, 2017·Journal of Basic and Clinical Physiology and Pharmacology·Nikola Hadzi-PetrushevMitko Mladenov
Oct 24, 2019·Archives of Toxicology·Hartmut JaeschkeWen-Xing Ding
Jul 24, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xuefu WangZhigang Tian
Jun 8, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anup RamachandranHartmut Jaeschke
Jul 18, 2015·Expert Review of Gastroenterology & Hepatology·Benjamin L Woolbright, Hartmut Jaeschke
Sep 15, 2018·International Journal of Molecular Sciences·Katrin NeumannGisa Tiegs
Jun 18, 2020·International Journal of Molecular Sciences·Roberta FuscoRosanna Di Paola
Mar 24, 2016·World Journal of Gastroenterology : WJG·Kuo Du, Hartmut Jaeschke
Nov 9, 2016·Archives of Toxicology·Michaël MaesMathieu Vinken
Jul 12, 2017·Cellular & Molecular Immunology·Hartmut Jaeschke
Jul 19, 2019·Experimental and Therapeutic Medicine·Akifumi KuwanoYoshihiro Ogawa
Jun 8, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Laurie D DeLeveHidekazu Tsukamoto

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