Schematic overview of proposed mechanisms (IMAGE)
Caption
Persistent HBV replication in hepatocytes may cause mitochondrial respiration dysfunction and further result in ROS accumulation. In response to elevated ROS levels, protein expression of Nrf-2 was increased, leading to transcriptional up-regulation of cytokines IL-6 and IL-8. Autocrine/paracrine IL-6 and IL-8 bound to their membrane receptors that recruited and activated Jak2. Then, Stat3 was recruited and subsequently phosphorylated by Jak2. Upon phosphorylation, p-Stat3 underwent homodimerization, allowing for translocation into the nucleus to promote transcriptional activation of a set of inflammatory genes, such as Saa1, S100a9, or Icam1. The surge of these inflammatory mediators caused sharply increased intrahepatic infiltration of immune and inflammatory cells, and then triggered the occurrence of liver inflammation. ROS scavenger N-NAC could decrease ROS production and suppress the process of ROS-triggered hepatic inflammation. NAC, N-acetylcysteine; ROS, reactive oxygen species; HBV, hepatitis B virus.
Credit
Rui Song, Shasha Yu, Xueyan Chen, Ning Ling, Dachuan Cai, Hong Ren, Min Chen
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CC BY-NC-ND