Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan.
Laboratory of Immunobiology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Miyagi, 980-8575, Japan.
Sci Rep. 2018 Feb 13;8(1):2911. doi: 10.1038/s41598-018-21014-8.
Nickel ions (Ni) are eluted from various metallic materials, such as medical devices implanted in human tissues. Previous studies have shown that Ni enters inflammatory cells inducing inflammation. However, the regulation of Ni uptake in cells has not yet been reported in detail. In the present study, we investigated the effects of various divalent cations on Ni uptake and Ni-induced interleukin (IL)-8 production in the human monocytic cell line, THP-1. We demonstrated that ZnCl MnCl, and CoCl inhibited the Ni uptake, while CuCl, FeCl, MgCl, and divalent metal transporter (DMT)-1 inhibitor, Chlorazol Black, did not. Furthermore, ZnCl inhibited Ni-induced IL-8 production, correlating with the inhibition of Ni uptake. These results suggested that Ni uptake occurred through Zn, Mn, and Co-sensitive transporters and that the inhibition of Ni uptake resulted in the inhibition of IL-8 production. Furthermore, using an Ni wire-implanted mouse model, we found that Ni wire-induced expression of mouse macrophage inflammatory protein-2 (MIP-2) and cyclooxygenase-2 (COX-2) mRNA in the skin tissue surrounding the wire were enhanced by low Zn conditions. These results suggested that the physiological concentration of Zn modulates Ni uptake by inflammatory cells, and a Zn deficient state might increase sensitivity to Ni.
镍离子（Ni）从各种金属材料中洗脱出来，例如植入人体组织中的医疗器械。先前的研究表明，Ni 进入炎症细胞会引发炎症。然而，细胞内 Ni 摄取的调节机制尚未详细报道。在本研究中，我们研究了各种二价阳离子对人单核细胞系 THP-1 中 Ni 摄取和 Ni 诱导的白细胞介素（IL）-8 产生的影响。结果表明，ZnCl、MnCl 和 CoCl 抑制 Ni 摄取，而 CuCl、FeCl、MgCl 和二价金属转运蛋白（DMT）-1 抑制剂 Chlorazol Black 则没有。此外，ZnCl 抑制 Ni 诱导的 IL-8 产生，与 Ni 摄取的抑制相关。这些结果表明，Ni 摄取是通过 Zn、Mn 和 Co 敏感转运体进行的，而 Ni 摄取的抑制导致了 IL-8 的产生抑制。此外，使用 Ni 丝植入小鼠模型，我们发现 Ni 丝周围皮肤组织中 Ni 丝诱导的小鼠巨噬细胞炎症蛋白-2（MIP-2）和环氧化酶-2（COX-2）mRNA 的表达在低 Zn 条件下增强。这些结果表明，生理浓度的 Zn 调节炎症细胞对 Ni 的摄取，而 Zn 缺乏状态可能会增加对 Ni 的敏感性。
