Hepatitis regulation by the inflammasome signaling pathway

Abstract

Hepatitis is damage and inflammation of the liver. It is triggered by both environmental and endogenous insults and is a platform for developing liver cirrhosis and cancer. Both innate and adaptive immune activation contribute to hepatic inflammation and disease. Viral hepatitis is the most common form of hepatitis and is typically associated with chronic viral infection. Alcohol-induced and non-alcoholic steatohepatitis are two rising hepatic problems. The innate immune inflammasome signaling cascade mediates the production of essential proinflammatory cytokines interleukin-1β (IL-1β) and IL-18. These cytokines regulate hepatic cell interaction and crosstalk of the various inflammatory pathways and influence disease outcome.

Extracellular vesicles released by hepatocytes from gastric infusion model of alcoholic liver disease contain a MicroRNA barcode that can be detected in blood

“…There are mainly two forms of circulating miRNAs: encapsulated miRNAs in EVs (EV‐miRNAs) and complex miRNA with noncoding RNA binding proteins known as Argonaute proteins (Ago‐miRNA) . Ago‐miRNA cannot integrate into recipient cells because of its size and lack of bioactivity for penetration, whereas EV‐miRNAs can efficiently penetrate recipient cells with their miRNAs . Our analysis identified 13 significantly up‐ or down‐regulated miRNAs in ASH HC‐EVs compared to control HC‐EVs.…”

The inflammasome: firing up innate immunity

“…Each of these important groups of pathogens is featured in one of the reviews in this issue. Negash and Gale provide an overview on the immunobiology and clinical importance of the inflammasome in liver diseases, with a particular emphasis on hepatitis B virus (HBV), hepatitis C virus (HCV), and non‐alcoholic fatty liver disease (NAFLD). The authors discuss the beneficial and detrimental properties of IL‐1 and IL‐18 production in HBV and HCV infections and speculate the possibility of using anti‐IL‐1 therapies as a potential treatment option.…”

Inflammation Mediated by JNK in Myeloid Cells Promotes the Development of Hepatitis and Hepatocellular Carcinoma

“…Consequently, reduced JNK signaling causes decreased expression of the M1-associated pro-inflammatory cytokines TNFα , IL1β , and IL6 (Han et al, 2013) and reduced expression of the M2-associated chemokines CCL17 and CCL22 (Hefetz-Sela et al, 2014). These observations are significant because TNFα , IL1β , and IL6 promote hepatic inflammation, hepatitis, and HCC development (Park et al, 2010; Negash and Gale, 2015) and CCL17/CCL22 can act as chemoattractants for tumor-associated Foxp3 + Tregs that regulate anti-tumor immunity (Nishikawa and Sakaguchi, 2010). Consequently, decreased expression of chemokines and inflammatory cytokines by JNK-deficient myeloid cells may contribute to reduced hepatic infiltration by inflammatory cells and the suppression of both hepatitis and HCC detected in Ø KO mice compared with Ø WT mice (Figure 3 & 4).…”