Oncotarget

Research Papers:

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

Hanchen Xu, Lei Wang, Peiyong Zheng, Yang Liu, Chunlei Zhang, Kaiping Jiang, Haiyan Song and Guang Ji _

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Oncotarget. 2017; 8:38914-38926. https://doi.org/10.18632/oncotarget.17153

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Abstract

Hanchen Xu1,*, Lei Wang1,*, Peiyong Zheng1,2, Yang Liu1, Chunlei Zhang1, Kaiping Jiang3, Haiyan Song1,2, Guang Ji1,2

1Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

2China-Canada Centre of Research for Digestive Diseases, Shanghai 200032, China

3Department 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.


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