Xiangya School of Public Health, Central South University, Changsha 410078, PR China.
Xiangya School of Public Health, Central South University, Changsha 410078, PR China.
Ecotoxicol Environ Saf. 2021 Dec 1;225:112779. doi: 10.1016/j.ecoenv.2021.112779. Epub 2021 Sep 13.
Polybrominated diphenyl ethers (PBDE-47), a kind of lipophilic persistent organic pollutants (POPs) brominated flame retardant, has been widely used in various consumer products. However, the toxicity of PBDE-47 on human immune system has not been well elucidated. Neutrophil extracellular traps (NETs) contribute to the innate immune responses, and the release of NETs is recognized as the most important part of the extracellular killing mechanism. The aim of this study was to investigate the effect of PBDE-47 on NETs and its possible molecular mechanism, as well as the intervention effect of curcumin (Cur). In this study, the formation of PBDE-47-induced NETs was observed by fluorescence microscopy and scanning electron microscopy, and was also quantitatively detected by DNA dye SYTOX green. In addition, we used Cur and Nrf2 inhibitor ML385 to explore the role of reactive oxygen species (ROS), extracellular signal regulated kinase (ERK) and p38 signaling pathway in PBDE-47-induced reticular formation. We demonstrated that PBDE-47 could significantly induce the formation of NETs, and its molecular mechanism might be related to ROS burst. Cur reduced ROS and inhibited PBDE-47-induced NETs formation by interfering with Nrf2. In conclusion, this study revealed that Cur hindered PBDE-47-induced NETs via Nrf2-associated ROS inhibition, which enriched the cytotoxicity mechanism of PBDE-47, and provided a new clue for the development of Cur as an antagonist of PBDE-47-related immune injury.
多溴二苯醚（PBDE-47）是一种亲脂性持久性有机污染物（POPs）溴代阻燃剂，已广泛应用于各种消费品中。然而，PBDE-47 对人体免疫系统的毒性尚未得到充分阐明。中性粒细胞胞外诱捕网（NETs）有助于先天免疫反应，而 NETs 的释放被认为是细胞外杀伤机制的最重要部分。本研究旨在探讨 PBDE-47 对 NETs 的影响及其可能的分子机制，以及姜黄素（Cur）的干预作用。在这项研究中，通过荧光显微镜和扫描电子显微镜观察 PBDE-47 诱导的 NETs 的形成，并通过 DNA 染料 SYTOX green 进行定量检测。此外，我们使用 Cur 和 Nrf2 抑制剂 ML385 来探讨活性氧（ROS）、细胞外信号调节激酶（ERK）和 p38 信号通路在 PBDE-47 诱导的网状形成中的作用。我们证明 PBDE-47 可以显著诱导 NETs 的形成，其分子机制可能与 ROS 爆发有关。Cur 通过干扰 Nrf2 减少 ROS 并抑制 PBDE-47 诱导的 NETs 形成。总之，本研究揭示了 Cur 通过 Nrf2 相关的 ROS 抑制来阻碍 PBDE-47 诱导的 NETs 的形成，丰富了 PBDE-47 的细胞毒性机制，并为开发 Cur 作为 PBDE-47 相关免疫损伤的拮抗剂提供了新的线索。
