Department of Laboratory Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Cancer Center of Fujian Medical University, Fujian Medical University Union Hospital, Fuzhou, China.
Mol Immunol. 2020 Jul;123:32-39. doi: 10.1016/j.molimm.2020.04.024. Epub 2020 May 12.
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.
目前，大多数关于乙型肝炎病毒（HBV）与 IL-33/ST2 轴关系的研究都集中在临床检测上，但 HBx 与 IL-33/ST2 轴调节和 Th 细胞功能调节的潜在分子机制尚未得到探索。本研究收集了慢性乙型肝炎（CHB）和 HBV 相关肝癌（HBV-HCC）患者以及健康对照者的血清样本，以及 HL7702-WT、HL7702-NC 和 HL7702-HBx 细胞的上清液，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 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无创诊断。HBx 通过 IL-33/ST2 轴促进肝细胞中 sST2 的表达，上调 Th2 细胞功能，抑制 Th1 细胞功能。HBx 与 GATA2 相互作用影响 ST2 启动子的活性。血清 sST2 检测是评估 HBV 传染病进展的宝贵指标，IL-33/ST2 轴在改变 HBV 感染引起的细胞免疫功能方面发挥着重要作用。
