Elevated serum A20 is associated with severity of chronic hepatitis B and A20 inhibits NF-κB-mediated inflammatory response

// Hanchen Xu 1, * , Lei Wang 1, * , Peiyong Zheng 1, 2 , Yang Liu 1 , Chunlei Zhang 1 , Kaiping Jiang 3 , Haiyan Song 1, 2 , Guang Ji 1, 2 1 Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China 2 China-Canada Centre of Research for Digestive Diseases, Shanghai 200032, China 3 Department of Hepatology, Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China * These authors have contributed equally to this work Correspondence to: Guang Ji, email: jiliver@vip.sina.com Haiyan Song, email: songhy@126.com Keywords: A20, chronic hepatitis B, serological biomarker, NF-κB, inflammation Received: February 14, 2017      Accepted: April 03, 2017      Published: April 17, 2017 ABSTRACT A20 is a powerful suppressor for inflammatory response. This study aims to determine A20 level in patients with chronic hepatitis B (CHB), and analyze its association with the disease severity. The role of A20 in inflammatory response was further investigated in vivo and in vitro . Our results showed significantly higher A20 in both serum and liver tissues in CHB patients than in health controls. Serum A20 level was positively correlated with ALT, AST and TNF-α. To induce hepatitis with inflammation and liver injury, mice were injected intraperitoneally with D-galactosamine (D-GalN), resulting in rapid increase of A20 in serum and liver tissues. Consistently, HepG2 and Huh-7 cells exposed to Lipopolysaccharide (LPS) or D-GalN were promoted to express A20. Moreover, overexpression or knockdown of A20 inhibited or increased TNF-α secretion separately. A20 significantly reduced pro-inflammatory cytokines expression and down-regulated phospho-IκBα and phospho-p65 in both cells. In conclusion, elevated A20 expression is involved in the severity of CHB, suggesting A20 to be a possible serological biomarker for the disease prognosis. Additionally, the inflammatory response is attenuated by A20 through inhibiting NF-κB activity, which partially contributes to the hepato-protective function of this molecule. Thus, up-regulating A20 might be a potential strategy for preventing the progress of CHB.