Abstract

Short-chain chlorinated paraffins (SCCPs) have been listed as a new class of persistent organic pollutants by the Stockholm Convention. SCCPs exhibit carcinogenic-, endocrine-, and metabolism-disrupting effects. However, the knowledge of the immunomodulatory effects of SCCPs and their underlying mechanisms, especially in specific immune cells, remains limited. In addition to SCCPs, C_9-13-CPs have also been detected in humans. In this study, murine RAW264.7 macrophages were exposed to C_9-13-CPs at environmentally relevant concentrations to investigate whether or how C_9-13-CPs exhibit immunomodulatory effects. The results showed that the exposure of RAW264.7 cells to C_9-13-CPs increased cell viability, as assayed by MTT analysis at 490 nm, and also promoted cell proliferation, as indicated by EdU uptake assay, which was measured at excitation and emission wavelengths of 488 and 512 nm, respectively. In addition, exposure to C_9-13-CPs not only led to elevated ATP level and intracellular Ca²⁺ level but also caused AMPK signaling activation and NF-κB signaling inhibition. Moreover, molecular docking showed that the β₂-AR receptor could bind to C_9-13-CPs. Taken together, these results suggest that the immune dysfunction of RAW264.7 cells caused by C_9-13-CPs is closely related to the β₂-AR/AMPK/NF-κB signaling axis.

中文翻译：

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评估 C9-13-CP 在巨噬细胞中的免疫调节作用

摘要

短链氯化石蜡（SCCPs）已被斯德哥尔摩公约列为一类新的持久性有机污染物。短链氯化石蜡表现出致癌、内分泌和代谢干扰作用。然而，关于短链氯化石蜡的免疫调节作用及其潜在机制（尤其是在特定免疫细胞中）的知识仍然有限。除短链氯化石蜡外，还在人体中检测到 C _9-13 -CPs。在这项研究中，将鼠 RAW264.7 巨噬细胞暴露于环境相关浓度的C _{9-13 -CP 以研究 C 9-13} -CP 是否或如何表现出免疫调节作用。结果表明RAW264.7细胞暴露于C _9-13-CPs 增加细胞活力，如通过 MTT 分析在 490 nm 处测定的那样，并且还促进细胞增殖，如 EdU 摄取测定所示，其分别在 488 和 512 nm 的激发和发射波长下测量。此外，暴露于 C _9-13 -CPs 不仅导致 ATP 水平和细胞内 Ca ²⁺水平升高，而且导致 AMPK 信号激活和 NF-κB 信号抑制。此外，分子对接表明β ₂ -AR 受体可以与C _9-13 -CPs 结合。综上所述，这些结果表明，C _{9-13 -CPs 引起的 RAW264.7 细胞免疫功能障碍与 β 2} -AR/AMPK/NF-κB 信号轴密切相关。