The contribution of sterile inflammation to the fatty liver disease and the potential therapies

Biomed Pharmacother. 2022 Apr:148:112789. doi: 10.1016/j.biopha.2022.112789. Epub 2022 Mar 7.

Abstract

Hepatic inflammation is prevalent in several metabolic liver diseases. Recent scientific advances about the pathogenesis of metabolic liver diseases showed an emerging role of several damage-associated molecular patterns (DAMPs), including DNA, high-mobility group box 1 (HMGB1), ATP and uric acid. For these DAMPs to induce inflammation, they should stimulate pattern recognition receptors (PRRs), which are located in the hepatic immune cells like resident Kupffer cells, infiltrated neutrophils, monocytes or dendritic cells. As a consequence, proinflammatory cytokines like interleukins (ILs)-1β and 18 alongside tumor necrosis factor (TNF)-α are overproduced and released, leading to pronounced hepatic inflammation and cellular death. This review highlights the contribution of these DAMPs and PRRs in the settings of alcoholic and nonalcoholic steatohepatitis. The review also summarizes the therapeutic usefulness of targeting NLR family pyrin domain containing 3 (NLRP3)-inflammasome, Toll-like receptors (TLRs) 4 and 9, IL-1 receptor (IL-1R), caspase 1, uric acid and GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) in these hepatic inflammatory disorders.

Keywords: DAMPs; NLRP3; PRRs; Steatohepatitis; Sterile inflammation.

Publication types

  • Review

MeSH terms

  • Adenosine Monophosphate
  • Alarmins / metabolism
  • Caspase 1 / metabolism
  • Guanosine Monophosphate / metabolism
  • Humans
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Liver Diseases, Alcoholic / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Pathogen-Associated Molecular Pattern Molecules / metabolism
  • Receptors, Pattern Recognition / metabolism
  • Receptors, Purinergic P2X7 / metabolism
  • Signal Transduction / physiology
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptor 9 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Uric Acid / metabolism

Substances

  • Alarmins
  • Inflammation Mediators
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Pathogen-Associated Molecular Pattern Molecules
  • Receptors, Pattern Recognition
  • Receptors, Purinergic P2X7
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha
  • Uric Acid
  • Adenosine Monophosphate
  • Guanosine Monophosphate
  • Caspase 1