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Human hepatocytes express absent in melanoma 2 and respond to hepatitis B virus with interleukin-18 expression

Author:
Pan, Xingfei, Xu, Haixia, Zheng, Changlong, Li, Mei, Zou, Xiaofang, Cao, Hong, Xu, Qihuan
Source:
Virus genes 2016 v.52 no.4 pp. 445-452
ISSN:
0920-8569
Subject:
DNA, Hepatitis B virus, Vaccinia virus, bacteria, chronic hepatitis B, cytoplasm, genome, hepatocytes, humans, immune response, inflammation, innate immunity, interleukin-18, interleukin-1beta, liver, melanoma, patients, receptors, viral antigens
Abstract:
Absent in melanoma 2 (AIM2) is a recently recognized cytoplasmic receptor which could sense cytoplasmic double-stranded DNA (dsDNA). After AIM2 detects the presence of parasitic nucleic acids (dsDNA) derived from invasive bacteria or viral genomes (for example, vaccinia virus and cytomegalovirus) within infected cells, AIM2 inflammasome could be formed. The formed AIM2 inflammasome could induce innate immune response and increase expressions of IL-1β and IL-18. Hepatitis B virus (HBV) is a hepatotropic, non-cytopathic double-stranded DNA virus. The immune response to viral antigens or virus is thought to be responsible for both liver damage and viral clearance in patients with HBV infection. However, there are no reports about whether AIM2 inflammasome exists in hepatocytes. In the present study, we investigated the presence and activity of AIM2 inflammasome in human hepatocytes. We found that AIM2 was expressed in cytoplasm of hepatocytes, and IL-18 expression was increased after AIM2 sensed HBV in hepatocytes in vitro. These results showed that AIM2 inflammasome was active in hepatocytes. We also found that hepatic AIM2 expression of chronic hepatitis B (CHB) patients was higher than that of controls. Hepatic AIM2 expression levels were positively correlated to the severity of liver inflammation. IL-18 is already considered to be associated with hepatic injury during HBV infection. In conclusion, we, therefore, believe that AIM2 inflammasome in hepatocytes might play an important role in the development and maintenance of HBV-related hepatitis.
Agid:
5238339