Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, China.
Ecotoxicol Environ Saf. 2021 Jun 1;215:112128. doi: 10.1016/j.ecoenv.2021.112128. Epub 2021 Mar 24.
Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macrophage RAW264.7. We assessed the effects of PFOA exposure on macrophage cell viability, cell apoptosis and cellular ROS level, and detected prominent cytokines release by RAW264.7. The results indicated that the cell viability of macrophage RAW264.7 was decreased by PFOA in dose- and time-dependent manners. Specifically, the exposure of 200 μM PFOA significantly increased apoptosis and ROS generation in macrophage, and thus caused cell damage. The ELISA results displayed that 100 μM PFOA exposure induced macrophage activation and enhanced cytokines secretion, including TNF-α, IL-1, IL-6, and IL-12. We also conducted nontargeted metabolomics based on LC-MS/MS and unveiled the perturbed metabolic pathways in macrophages induced by sublethal doses of PFOA (10 μM and 100 μM). Remarkably, global metabolomics results displayed that 10 μM PFOA exposure affected glutamine related pathways and the exposure at 100 μM conspicuously changed glutathione and fatty acid oxidation metabolism. These findings showed that 10 μM PFOA exposure could impel metabolic reprogramming of macrophage to trigger inflammatory response, although such dose displayed no obvious effect on cell viability, cellular ROS or apoptosis events of macrophage RAW264.7.
全氟辛酸（PFOA）是工业中最常用的全氟化学品之一。近年来，人们对 PFOA 毒性的广泛关注日益增加。然而，关于 PFOA 的免疫毒性的报告却相当有限。本研究旨在探讨 PFOA 暴露对巨噬细胞 RAW264.7 的免疫毒性。我们评估了 PFOA 暴露对巨噬细胞细胞活力、细胞凋亡和细胞 ROS 水平的影响，并检测了 RAW264.7 细胞中明显的细胞因子释放。结果表明，PFOA 以剂量和时间依赖的方式降低巨噬细胞 RAW264.7 的细胞活力。具体来说，200 μM PFOA 的暴露显著增加了巨噬细胞的凋亡和 ROS 生成，从而导致细胞损伤。ELISA 结果显示，100 μM PFOA 暴露诱导巨噬细胞活化并增强细胞因子分泌，包括 TNF-α、IL-1、IL-6 和 IL-12。我们还基于 LC-MS/MS 进行了非靶向代谢组学研究，揭示了亚致死剂量的 PFOA（10 μM 和 100 μM）诱导巨噬细胞中失调的代谢途径。值得注意的是，全局代谢组学结果显示，10 μM PFOA 暴露影响谷氨酰胺相关途径，而 100 μM 的暴露则明显改变谷胱甘肽和脂肪酸氧化代谢。这些发现表明，10 μM PFOA 暴露可以促使巨噬细胞进行代谢重编程，从而引发炎症反应，尽管这种剂量对巨噬细胞 RAW264.7 的细胞活力、细胞 ROS 或凋亡事件没有明显影响。
