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

Elevated serum A20 is associated with severity of chronic hepatitis B and A20 inhibits NF-κB-mediated inflammatory response.
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血清 A20 升高与慢性乙型肝炎的严重程度相关,并且 A20 抑制 NF-κ B 介导的炎症反应

DOI:
10.18632/oncotarget.17153
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发表时间:
2017-06-13
期刊:
影响因子:
--
通讯作者:
Ji G
Ji G
中科院分区:
其他
文献类型:
--
作者:
Xu H;Wang L;Zheng P;Liu Y;Zhang C;Jiang K;Song H;Ji G

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A20是炎症反应的强大抑制剂。本研究旨在检测慢性B型肝炎(CH B)患者血清A20水平,并分析其与疾病严重程度的关系。在体内和体外进一步研究A20在炎症反应中的作用。我们的研究结果表明,在慢性乙型肝炎患者血清和肝组织中的A20显着高于健康对照组。血清A20水平与ALT、AST、TNF-α呈正相关。为了诱导伴有炎症和肝损伤的肝炎,小鼠腹腔注射D-氨基半乳糖(D-GalN),导致血清和肝组织中A20迅速增加。同时,脂多糖(LPS)或D-半乳糖胺(D-GalN)可促进HepG 2和Huh-7细胞表达A20。此外,A20的过表达或敲低分别抑制或增加TNF-α的分泌。A20显著降低两种细胞中促炎细胞因子的表达,并下调磷酸化I κBα和磷酸化p65。总之,A20表达升高与CHB的严重程度有关,提示A20可能是疾病预后的血清学生物标志物。此外,A20通过抑制NF-κB活性减弱炎症反应,这部分有助于该分子的肝脏保护功能。因此,上调A20可能是预防CHB进展的潜在策略。
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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