Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
Department of Nutrition and Hygiene, School of Public Health, Nanyong University, Nantong, Jiangsu 226001, People's Republic of China.
Neurotoxicol Teratol. 2018 May-Jun;67:65-75. doi: 10.1016/j.ntt.2018.03.004. Epub 2018 Mar 22.
Perfluorooctane sulfonate (PFOS) is a persistent and bioaccumulative compound that has been widely used in various fields of life and industrial productions, because of its special chemical and physical properties. Numerous studies have indicated significant neurotoxic effect of PFOS, especially on neurons and microglia. However, the influence of PFOS on astrocyte physiology remains unclear. In this study, we showed that PFOS triggered reactive astrocytosis in time- and dose-dependent manners. The low-doses of PFOS increased the cell number and the expression of glial fibrillary acidic protein (GFAP), a well-known hallmark of reactive astrocytes, in C6 astrocyte cells. ELISA and RT-PCR analysis showed that PFOS promoted the expression and secretion of Interleukin-1 beta (IL-1β) in dose- and time-dependent manners. Furthermore, PFOS exposure could induce the phosphorylation and degradation of IκBα, and the translocation of NF-κB p65 from the cytoplasm to the nucleus in C6 glioma cell line. Thus, the NF-кB signaling pathway can be activated after PFOS exposure. In addition, pretreatment with AKT inhibitor LY294002 could obviously attenuate PFOS-induced NF-κB activation and IL-1β secretion. Taken together, these results indicated that PFOS could facilitate reactive astrocytosis and the secretion of pro-inflammatory cytokines through AKT-dependent NF-κB signaling pathway.
全氟辛烷磺酸 (PFOS) 是一种持久性且生物累积的化合物，由于其特殊的化学和物理性质，已广泛应用于生活和工业生产的各个领域。大量研究表明 PFOS 具有显著的神经毒性作用，尤其是对神经元和小胶质细胞。然而，PFOS 对星形胶质细胞生理学的影响尚不清楚。在这项研究中，我们表明 PFOS 以时间和剂量依赖的方式触发反应性星形胶质细胞增生。低剂量的 PFOS 增加了 C6 星形胶质细胞中细胞数量和神经胶质纤维酸性蛋白 (GFAP) 的表达，GFAP 是反应性星形胶质细胞的一个众所周知的标志物。ELISA 和 RT-PCR 分析表明，PFOS 以剂量和时间依赖的方式促进白细胞介素-1β (IL-1β) 的表达和分泌。此外，PFOS 暴露可诱导 C6 神经胶质瘤细胞系中 IκBα 的磷酸化和降解，以及 NF-κB p65 从细胞质向细胞核的易位。因此，NF-κB 信号通路可在 PFOS 暴露后被激活。此外，AKT 抑制剂 LY294002 的预处理可明显减弱 PFOS 诱导的 NF-κB 激活和 IL-1β 分泌。综上所述，这些结果表明 PFOS 可通过 AKT 依赖性 NF-κB 信号通路促进反应性星形胶质细胞增生和促炎细胞因子的分泌。
