School of Medical Technology and Information Engineering, Zhenjiang Chinese Medical University, Hangzhou 310053, China.
School of Medical Technology and Information Engineering, Zhenjiang Chinese Medical University, Hangzhou 310053, China.
Ecotoxicol Environ Saf. 2023 Feb;251:114520. doi: 10.1016/j.ecoenv.2023.114520. Epub 2023 Jan 12.
Increasing amounts of nanoplastics (NPs) in the environment are a great threat to human health, causing intestinal inflammation when consumed through seafood and water. There is, however, still a lack of understanding of the immunomodulatory role of NPs in immune cells, especially the early signal events behind inflammation resulting from NPs ingestion. In this study, we explored the dynamic internalization of polystyrene NPs and their carboxy and amino-functionalized products (PS, PS-COOH and PS-NH) followed by activation of ROS-MAPK/NF-κB signaling pathways in macrophage RAW 264.7. The inflammatory and cytotoxic potentials of NPs were evaluated by ELISA and apoptosis assays. Results showed that PS-COOH accumulated most in cells and induced more pronounced ROS and apoptosis than PS, PS-NH and PS-μm. PS-COOH and PS-NH showed stronger MAPK/NF-κB activation potential to at a low concentration of 10 μg/mL than unmodified PS, followed by production of IL-6 and TNF-α cytokines. Furthermore, PS-COOH induced MAPK/NF-κB activation and cytokine secretion could be inhibited by NAC, indicating that ROS was responsible for signal dysregulation and immunogenicity of PS-COOH, but not for PS-NH. The results suggested that the MAPK and NF-κB pathways were involved in NPs-induced macrophage inflammation, which was influenced by surface functionalization of NPs, with carboxylated PS NPs exhibiting a greater pro-inflammatory and cytotoxic potential.
环境中纳米塑料（NPs）的含量不断增加，对人类健康构成了巨大威胁，通过海鲜和水摄入后会引起肠道炎症。然而，人们对 NPs 在免疫细胞中的免疫调节作用仍缺乏了解，特别是对 NPs 摄入引起炎症的早期信号事件知之甚少。在这项研究中，我们探索了聚苯乙烯 NPs 及其羧基和氨基功能化产物（PS、PS-COOH 和 PS-NH）在巨噬细胞 RAW 264.7 中的动态内化，以及 ROS-MAPK/NF-κB 信号通路的激活。通过 ELISA 和细胞凋亡实验评估了 NPs 的炎症和细胞毒性潜力。结果表明，PS-COOH 在细胞中积累最多，并诱导比 PS、PS-NH 和 PS-μm 更明显的 ROS 和凋亡。PS-COOH 和 PS-NH 在低浓度 10μg/mL 时就显示出比未修饰 PS 更强的 MAPK/NF-κB 激活潜力，随后产生 IL-6 和 TNF-α 细胞因子。此外，PS-COOH 诱导的 MAPK/NF-κB 激活和细胞因子分泌可被 NAC 抑制，表明 ROS 负责 PS-COOH 的信号失调和免疫原性，但对 PS-NH 则不然。结果表明，MAPK 和 NF-κB 途径参与了 NPs 诱导的巨噬细胞炎症，这受到 NPs 表面功能化的影响，其中羧化 PS NPs 表现出更大的促炎和细胞毒性潜力。
