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

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.

Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases

“…Previous studies measuring TNFAIP3 in the serum using ELISA assays have been performed in the context of viral infections such as chronic Hepatitis B infections 22 . To confirm that alterations in TNFAIP3 transcription corresponded with translation into the TNFAIP3 protein, we tested serum levels of TNFAIP3 in MOG-AAD patients.…”

Interference of Apoptosis by Hepatitis B Virus

“…Further studies show that the death receptor TRAIL-R5 expression is enhanced by HBX in Huh-7 cells through the activation of the NF-κB pathway, which contributes to the increased apoptosis induced by TRAIL [ 74 ]. Although A20 is upregulated in HBV-infected HCC cells, liver tissue, and serum of chronic HBV-infected patients [ 80 , 153 ], HBX overexpression in hepatocytes leads to A20 reduction [ 154 ]. HBX sensitizes the hepatocytes to the TRAIL-induced apoptosis by repressing the A20 expression and its ubiquitin ligase activity ( Figure 2 ) [ 154 ].…”

A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage

“…[7,8] A20, also known as tumor necrosis factor α-inducible protein 3, possesses inflammation-inhibitory effects by depressing the activation of nuclear factor-kappa B (NF-κB) [9] and may act as an endogenous protective factor in some inflammatory diseases, including acute myocardial infarction, chronic hepatitis B, and rheumatoid arthritis. [10][11][12] A20 expression was dramatically up-regulated in damaged brain tissues following experimental head trauma or intracerebral hemorrhage. [13,14] Exogenous supplementation with A20 could significantly inhibit neuroinflammation, reduce brain edema, decrease blood-brain barrier disruption, and improve neurological function in rats after hemorrhagic stroke or traumatic brain injury, indicating that A20 may have a neuroprotective effect on acute brain injury ( ABI).…”