Abstract
Cell death and inflammation are two central elements in the development of liver fibrosis.
Inflammasomes are intracellular multiprotein complexes expressed in both hepatocytes
and nonparenchymal cells in the liver that are key regulators of inflammation and
cell fate. They respond to cellular danger signals by activating caspase 1, releasing
the proinflammatory cytokines IL-1β and IL-18, as well as initiating a novel pathway
of programmed cell death termed “pyroptosis.” These processes can initiate and perpetuate
an abnormal wound-healing response with the principle cellular target being the activation
of hepatic stellate cells. From the various inflammasomes, the NLRP3 inflammasome
has been increasingly implicated in the pathogenesis of chronic inflammatory liver
diseases, including nonalcoholic steatohepatitis, a disease process that is soaring
and has evolved as a primary cause of liver fibrosis and need for liver transplantation.
In this review, the authors highlight the growing evidence for both indirect and direct
effects of inflammasomes in triggering liver fibrosis as well as potential novel targets
for antifibrotic therapies.
Keywords
liver disease - fibrosis - hepatic stellate cells - cell death - danger-associated
molecular patterns - pattern recognition receptors - inflammation - therapy - nonalcoholic
steatohepatitis
