Inflammasome activation in the liver: Focus on alcoholic and non-alcoholic steatohepatitis

Clin Res Hepatol Gastroenterol. 2015 Sep:39 Suppl 1:S18-23. doi: 10.1016/j.clinre.2015.06.012. Epub 2015 Jul 26.

Abstract

Upregulation of the inflammatory cascade is a major element both in the progression of steatohepatitis to severe alcoholic hepatitis as well as in the progression of NASH to advanced NASH with fibrosis. The mechanisms underpinning these changes are only partially understood. Activation of the inflammatory cascade requires multiple stimuli and in this report, we discuss the role of inflammasomes that activate IL-1β as well as the sterile and pathogen-derived danger signals that results in inflammasome activation and inflammation in alcoholic and non-alcoholic steatohepatitis. The dynamics of inflammasome activation, the cell types involved and the trigger signals appear to be somewhat different between ASH and NASH. Further studies are needed to dissect the pathology-related differences between these two major forms of steatohepatitis. Clinical and therapeutic implications of inflammasome activation in steatohepatitis are also discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Enzyme Inhibitors / therapeutic use
  • Fatty Liver / drug therapy
  • Fatty Liver / metabolism*
  • Humans
  • Inflammasomes / metabolism*
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1beta / metabolism
  • Liver / metabolism
  • Liver Diseases, Alcoholic / drug therapy
  • Liver Diseases, Alcoholic / metabolism
  • Up-Regulation

Substances

  • Enzyme Inhibitors
  • Inflammasomes
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta