Pyroptosis in Liver Disease: New Insights into Disease Mechanisms

There has been increasing interest in pyroptosis as a novel form of pro-inflammatory programmed cell death. The mechanism of pyroptosis is significantly different from other forms of cell death in its morphological and biochemical features. Pyroptosis is characterized by the activation of two different types of caspase enzymes—caspase-1 and caspase-4/5/11, and by the occurrence of a proinflammatory cytokine cascade and an immune response. Pyroptosis participates in the immune defense mechanisms against intracellular bacterial infections. On the other hand, excessive inflammasome activation can induce sterile inflammation and eventually cause some diseases, such as acute or chronic hepatitis and liver fibrosis. The mechanism and biological significance of this novel form of cell death in different liver diseases will be evaluated in this review. Specifically, we will focus on the role of pyroptosis in alcoholic and non-alcoholic fatty liver disease, as well as in liver failure. Finally, the therapeutic implications of pyroptosis in liver diseases will be discussed.