East China University of Science and Technology, School of Pharmacy, Department of Pharmaceutical Sciences, Shanghai 200237, China; East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, Shanghai 200237, China.
East China University of Science and Technology, School of Pharmacy, Department of Pharmaceutical Sciences, Shanghai 200237, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2018 Dec;214:36-42. doi: 10.1016/j.cbpc.2018.08.010. Epub 2018 Sep 3.
Environmental exposure to arsenic is known to induce immunotoxicity. Macrophages are the professional phagocytes that are important in the immune system. In this study, we utilized the macrophages derived from the THP-1 human monocyte cell line as the experimental model to study the functional suppression induced by arsenite (As), one of the most prevalent forms of inorganic arsenic, at environmentally-relevant concentrations. Apoptosis was observed in the THP-1 derived macrophages treated with 500 nM As for 18 h. Suppression of phagocytosis was induced by 18 h As treatment starting from 100 nM. Suppressive effects on the production of two pro-inflammatory cytokines, IL-1β and TNF-α, were also found with the treatment of low to moderate doses of As in lipopolysaccharides-stimulated THP-1 derived macrophages. The nitric oxide production was also inhibited by As treatments, which was negatively correlated with the production of superoxide. Collectively, the results from the study demonstrated that environmentally-relevant concentrations of As induced cytotoxicity and suppressed the major cellular functions in THP-1 derived macrophages. The macrophages were showed to be relatively sensitive to As, and could be the essential target of the toxicity induced by environmental arsenic exposures.
环境砷暴露已知会诱导免疫毒性。巨噬细胞是免疫系统中重要的专业吞噬细胞。在这项研究中,我们利用 THP-1 人单核细胞系来源的巨噬细胞作为实验模型,研究亚砷酸盐(As)的功能抑制作用,As 是最常见的无机砷形式之一,在环境相关浓度下。用 500 nM As 处理 18 小时后,在 THP-1 衍生的巨噬细胞中观察到细胞凋亡。从 100 nM 开始的 18 小时 As 处理诱导吞噬作用抑制。在脂多糖刺激的 THP-1 衍生巨噬细胞中,用低至中等剂量的 As 处理也发现了对两种促炎细胞因子 IL-1β 和 TNF-α 的产生的抑制作用。As 处理还抑制了一氧化氮的产生,这与超氧化物的产生呈负相关。总的来说,研究结果表明,环境相关浓度的 As 诱导了 THP-1 衍生巨噬细胞的细胞毒性,并抑制了其主要细胞功能。巨噬细胞对 As 相对敏感,可能是环境砷暴露引起毒性的重要靶细胞。