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Hepatitis B virus X protein (HBx) promotes ST2 expression by GATA2 in liver cells.
Molecular Immunology ( IF 3.6 ) Pub Date : 2020-05-12 , DOI: 10.1016/j.molimm.2020.04.024
Siyan Chen 1 , Luxi Wu 2 , Lirong Peng 2 , Xiaoqian Wang 2 , Nanhong Tang 3
Affiliation  

At present, most studies on the relationship between hepatitis B virus (HBV) and IL-33/ST2 axis focus on clinical detection, but the underlying molecular mechanisms of HBx and IL-33/ST2 axis regulation and Th cell function regulation have not been explored. In this study, serum samples of patients with chronic hepatitis B (CHB) and HBV-related liver cancer (HBV-HCC), and healthy controls, as well as the supernatant solutions of HL7702-WT, HL7702-NC, and HL7702-HBx cells were collected to detect the content of soluble ST2 (sST2). The contents of Th1 cytokines (TNF-α and TNF-γ) and Th2 cytokines (IL-6 and IL-10) in the supernatant of different co-culture groups were detected. The effects of GATA2 on ST2 promoter transcription were investigated by upregulation or interference with GATA2 expression, dual-luciferase reporting, and ChIP experiments. The combined detection of sST2 and FIB-4 was beneficial to the non-invasive diagnosis of liver fibrosis. HBx promotes sST2 expression in liver cells, upregulates Th2 cell function, and inhibits Th1 cell function through IL-33/ST2 axis. HBx interacts with GATA2 to influence the activity of ST2 promoter. Serum sST2 detection is an invaluable indicator for the assessment of the progress of HBV infectious diseases, and the IL-33/ST2 axis plays an important role in changing the cellular immune function caused by HBV infection.

中文翻译:

乙型肝炎病毒X蛋白(HBx)通过肝细胞中的GATA2促进ST2表达。

目前,关于乙型肝炎病毒(HBV)与IL-33 / ST2轴之间关系的大多数研究都集中在临床检测上,但是尚未了解HBx和IL-33 / ST2轴调控和Th细胞功能调控的潜在分子机制。探索。在这项研究中,慢性乙型肝炎(CHB)和HBV相关肝癌(HBV-HCC)患者的血清样本以及健康对照者,以及HL7702-WT,HL7702-NC和HL7702-HBx的上清液收集细胞以检测可溶性ST2(sST2)的含量。检测不同共培养组上清液中Th1细胞因子(TNF-α和TNF-γ)和Th2细胞因子(IL-6和IL-10)的含量。通过上调或干扰GATA2表达,双荧光素酶报告和ChIP实验研究了GATA2对ST2启动子转录的影响。sST2和FIB-4的联合检测有利于肝纤维化的非侵入性诊断。HBx通过IL-33 / ST2轴促进肝细胞中sST2的表达,上调Th2细胞的功能,并抑制Th1细胞的功能。HBx与GATA2相互作用以影响ST2启动子的活性。血清sST2检测是评估HBV感染性疾病进展的重要指标,IL-33 / ST2轴在改变由HBV感染引起的细胞免疫功能中起着重要作用。
更新日期:2020-05-12
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