Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
Inflammation. 2015 Oct;38(5):1823-34. doi: 10.1007/s10753-015-0160-y.
Hepatitis C virus (HCV) is a major cause of chronic liver disease and has led to cirrhosis or hepatocellular carcinoma in a majority of infected individuals. We have previously demonstrated that the HCV alternate reading frame protein (F protein) is related to Th1/Th2 bias in chronic hepatitis C (CHC) patients, and we aimed to explore the relative molecular mechanisms here. A total of 104 cases including CHC patients and healthy donors were enrolled. T-bet and GATA-3 expression levels were analyzed in peripheral blood mononuclear cells (PBMCs). The levels of signal transducer and activator of transcription-1/-6(STAT1/6) and phosphorylated STAT1/6(pSTAT1/6) in PBMCs were measured by Western blotting. Our results showed that the levels of T-bet in PBMCs, as well as the levels of gamma interferon (IFN-γ) in sera, were decreased in anti-F protein antibody seropositive patients compared with anti-F protein antibody seronegative patients, whereas the levels of GATA-3 did not show difference between the two groups. Moreover, the decreased pSTAT1 and increased pSTAT6 were observed in PBMCs by HCV core/F protein stimulation with constant STAT1/6 expression. Taken together, it suggested that T-bet may be involved in Th1/Th2 bias induced by HCV F protein, and the disruption of STAT phosphorylation may participate in this mediation.
丙型肝炎病毒（HCV）是慢性肝病的主要病因，在大多数感染个体中可导致肝硬化或肝细胞癌。我们之前已经证明，HCV 读码框蛋白（F 蛋白）与慢性丙型肝炎（CHC）患者的 Th1/Th2 偏向有关，我们旨在在此探讨相关的分子机制。共纳入 104 例包括 CHC 患者和健康供体的病例。分析外周血单个核细胞（PBMC）中的 T 细胞转录激活因子（T-bet）和 GATA 结合蛋白-3（GATA-3）表达水平。通过 Western blot 法测定 PBMC 中信号转导和转录激活因子-1/-6（STAT1/6）和磷酸化 STAT1/6（pSTAT1/6）的水平。结果显示，与抗 F 蛋白抗体阴性患者相比，抗 F 蛋白抗体阳性患者的 PBMCs 中 T-bet 水平以及血清中γ干扰素（IFN-γ）水平降低，而两组之间 GATA-3 水平无差异。此外，通过 HCV 核心/F 蛋白刺激，观察到 PBMCs 中 pSTAT1 减少和 pSTAT6 增加，而 STAT1/6 表达保持不变。总之，这表明 T-bet 可能参与了 HCV F 蛋白诱导的 Th1/Th2 偏向，STAT 磷酸化的破坏可能参与了这种介导作用。
