Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.1
Peer-review started: November 9, 2017
First decision: December 4, 2017
Revised: December 21, 2017
Accepted: January 15, 2018
Article in press: January 15, 2018
Published online: January 27, 2018
Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus (HCV) infection, and sterile stressors (oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro- or anti-apoptotic. Acute and chronic liver diseases are cytokine-driven diseases as several proinflammatory cytokines (IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HCV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HCV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases.
Core tip: Inflammasomes are newly recognized vital players in innate immunity. Several factors have been identified able to activate the NLRP3 inflammasome. Inappropriate activation of NLRP3 can contribute to the onset and progression of various diseases, particularly age-related diseases. It is well established that hepatitis C virus infection plays a critical role in the promotion of liver inflammation and disease, inducing the production of IL-1β and the activation of NLRP3. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and lately, hepatocellular carcinoma. In non-alcoholic fatty liver disease, the regulation of inflammation processes may prevent the progression of non-alcoholic steatohepatitis to fibrosis.