Xia Shiqing, Sun Qian, Zou Zhonglan, Liu Yonglian, Fang Xiaolin, Sun Baofei, Wei Shaofeng, Wang Dapeng, Zhang Aihua, Liu Qizhan
The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou, People's Republic of China.
Center for Global Health, China International Cooperation Center for Environment and Human Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Int J Biol Sci. 2020 Jan 1;16(3):483-494. doi: 10.7150/ijbs.39351. eCollection 2020.
Endemic arsenicosis is a public health problem that affects thousands of people worldwide. However, the biological mechanism involved is not well characterized, and there is no specific treatment. Exposure to arsenic may be associated with immune-related problems. In the present work, we performed an investigation to determine whether the Th17/Treg balance was abnormal in peripheral blood mononuclear cells (PBMCs) of patients with arsenicosis caused by burning coal. Furthermore, we investigated the effect of extract (GBE) on the Th17/Treg imbalance in patients with arsenicosis. In this trial, 81 arsenicosis patients and 37 controls were enrolled. The numbers of Th17 and Treg cells, as well as related transcription factors and serum cytokines, were determined at the beginning and end of the study. Patients with arsenicosis exhibited higher levels of Th17 cells, Th17-related cytokines (IL-17A and IL-6), and the transcription factor RORγt. There were lower levels of Treg cells, a Treg-related cytokine (IL-10), and the transcription factor Foxp3 as compared with controls. There was a positive correlation between the levels of Th17 cells and IL-17A and the levels of arsenic in hair. Arsenicosis patients were randomly assigned to a GBE treatment group or a placebo group. After 3 months of follow-up, 74 patients completed the study (39 cases in the GBE group and 35 in the placebo group). Administration of GBE to patient upregulated the numbers of Treg cells and the level of IL-10 and downregulated the numbers of Th17 cells and the levels of cytokines associated with Th17 cells. The mRNA levels of Foxp3 and RORγt were increased and decreased, respectively. These results indicated that exposure to arsenic is associated with immune-related problems. The present investigation describes a previously unknown mechanism showing that an imbalance of pro- and anti-inflammatory T cells is involved in the pathogenesis of arsenicosis and that a GBE exerts effects on arsenicosis through regulation of the pro- and anti-inflammatory T cell balance.
地方性砷中毒是一个影响全球数千人的公共卫生问题。然而,其中涉及的生物学机制尚未得到充分阐明,且尚无特效治疗方法。砷暴露可能与免疫相关问题有关。在本研究中,我们进行了一项调查,以确定燃煤型砷中毒患者外周血单个核细胞(PBMCs)中Th17/Treg平衡是否异常。此外,我们还研究了银杏叶提取物(GBE)对砷中毒患者Th17/Treg失衡的影响。在该试验中,纳入了81例砷中毒患者和37例对照。在研究开始和结束时测定Th17和Treg细胞的数量以及相关转录因子和血清细胞因子。砷中毒患者的Th17细胞、Th17相关细胞因子(IL-17A和IL-6)以及转录因子RORγt水平较高。与对照组相比,Treg细胞、Treg相关细胞因子(IL-10)和转录因子Foxp3水平较低。Th17细胞和IL-17A水平与头发中的砷含量呈正相关。砷中毒患者被随机分为GBE治疗组或安慰剂组。经过3个月的随访,74例患者完成了研究(GBE组39例,安慰剂组35例)。给患者服用GBE上调了Treg细胞数量和IL-10水平,下调了Th17细胞数量以及与Th17细胞相关的细胞因子水平。Foxp3和RORγt的mRNA水平分别升高和降低。这些结果表明砷暴露与免疫相关问题有关。本研究描述了一种先前未知的机制,表明促炎和抗炎T细胞失衡参与了砷中毒的发病机制,且GBE通过调节促炎和抗炎T细胞平衡对砷中毒发挥作用。