锌对THP-1细胞自噬、NF-κB通路活化及产生白细胞介素23的影响

Effects of Zinc on autophagy, NF-κB pathway, and IL-23 production of THP-1 cell

目的从调节自噬、NF-κB和IL-23的角度研究锌对炎症的影响及机制。方法检测锌对静息及LPS刺激的THP-1的增殖及凋亡、自噬相关蛋白水平、NF-κB p65及其磷酸化水平以及IL-23表达的影响,并探讨各指标间的关联。结果锌可轻度促进THP-1细胞凋亡、抑制其增殖,效应与浓度有关;总体上增强THP-1自噬,但在LPS刺激时、高浓度锌抑制自噬。锌可提高NF-κB p65磷酸化;可增高IL-23、但高浓度时抑制IL-23。结论锌可活化THP-1的NF-κB通路、并以剂量依赖的方式调节自噬、增殖、凋亡及IL-23的产生且各指标密切关联。提示锌的作用机制复杂,对其临床适用症及剂量应认真控制。

This study was designed to investigate whether the regulation of autophagy, NF-κB, and IL-23 involve in the anti-inflammatory effects of zinie and the underline mechanisms. Resting and LPS-stimulated THP-1 cells were used to evaluate the effects of zinc sulfate on the proliferation and death of THP-1, the levels of autophagy-associated proteins （Beclinl, p62/SQSTM1, and ratio of LC3B II/I）, the NF-κB p65 phosphorylation, and the IL-23 levels. Data showed that zinc exerted a dose-dependant effect on both the proliferation and death of THP-1, and its dose-effect relationship was altered by the LPS-stimulation. In general, ZnSO4 augmented the autophagy except that in the presence of LPS-stimulation, while high-concentration （100 μmol/L） of ZnSO4 suppressed the autophagy of THP-1; ZnSO4 also increased the phosphorylation of NF-κB p65 and the production of IL-23, while the 100 μmol/L of ZnSO4 suppressed the IL-23 production. Taken tagether, Zinc activates the NF-κB p65 pathway in THP-1 cells, and regulates the autophagy, proliferation and death, and the IL-23 production of THP-1 cells in a dose-dependant manner, and these parameters are tightly interacted, thus, the clinical usage and dose of zinic should be treated with caution.