State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
Sci Total Environ. 2017 Aug 15;592:357-365. doi: 10.1016/j.scitotenv.2017.03.035. Epub 2017 Mar 17.
As an important structural analogue of bisphenol A (BPA), bisphenol S (BPS) has been used as alternatives to BPA in industrialized production. However, the immunotoxicity of BPS remains poorly understood. As a critical model in inflammatory responses, macrophages are used to explore the immunotoxic potential and mechanisms of BPS at environmentally relevant concentrations in our study. Here, we are combining molecular toxicology and mass spectrometry (MS)-based global metabolomics and lipidomics study together to estimate the variation of cytokines profiling and metabolism characteristic following BPS exposure. Our results demonstrated that BPS exposure induced pro-inflammatory phenotype by activating the immuno-related cytokines which include TNF-α, IL-1β and IL-6, modulating metabolic pathways which include glycolytic, glutathione (GSH), sphingomyelin (SM)-ceramide (Cer), glycerophospholipids (GPs) and glycerolipids (GLs). These toxicological mechanisms are providing us with a deeper understanding of the critical role of metabolites and lipids reprogramming in immunotoxicity of BPS.
作为双酚 A（BPA）的重要结构类似物，双酚 S（BPS）已被用作工业化生产中 BPA 的替代品。然而，BPS 的免疫毒性仍知之甚少。作为炎症反应的重要模型，本研究中我们使用巨噬细胞来探索环境相关浓度下 BPS 的免疫毒性潜力和机制。在这里，我们将分子毒理学和基于质谱（MS）的全局代谢组学和脂质组学研究结合在一起，以评估 BPS 暴露后细胞因子谱和代谢特征的变化。我们的结果表明，BPS 通过激活 TNF-α、IL-1β 和 IL-6 等与免疫相关的细胞因子，以及调节糖酵解、谷胱甘肽（GSH）、鞘磷脂（SM）-神经酰胺（Cer）、甘油磷脂（GPs）和甘油脂（GLs）等代谢途径，诱导了促炎表型。这些毒理学机制使我们对代谢物和脂质重编程在 BPS 免疫毒性中的关键作用有了更深入的了解。
