Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, WenhuaXi Road, Jinan, 250012, Shandong, People's Republic of China.
Mol Biol Rep. 2013 Aug;40(8):4979-84. doi: 10.1007/s11033-013-2598-z. Epub 2013 May 18.
Zinc is the most common trace mineral after iron in the human body. In organisms, zinc transporters help zinc influx and efflux from cells. A previous study has reported that Zip2 was up-regulated over 27-fold in human monocytic THP-1 cells, when intracellular zinc was depleted by TPEN. Our study found Zip2 was over-expressed in leukocytes of asthmatic infants, especially those in which the serum zinc level was lower than those in healthy infants. Pulmonary tuberculosis (PTB) patients have significantly low serum zinc levels. Here we investigated whether Zip2 level was changed in the patients with PTB. Zip2 mRNA and protein levels in peripheral blood mononuclear cells (PBMC) from PTB (n1=23) and healthy controls (n2=42) were detected by quantitative real-time PCR and western blot, respectively. mRNA expression levels of another four zinc transporters, Zip1, Zip6, Zip8 and ZnT1, were detected by quantitative real-time PCR. Zip2 mRNA level was significantly up-regulated in PTB patients (P=0.001), and Zip8 mRNA level was significantly down-regulated compared with control individuals (P<0.001). In contrast, there were no significant changes in mRNA levels of Zip1, Zip6 and ZnT1 in either group (P>0.05). Zip2 protein expression levels increased in PTB patients compared with control individuals. Our study found that knockdown of ZIP2 with siRNA caused a decrease in Zip2 levels in PBMC of PTB patients, while reducing the expression of INF-γ (P<0.01) and increasing the expression of IL-6(P<0.01). These data provide evidence that increased expression of Zip2 gene is closely associated with immunity of PTB patients, suggesting that the Zip2 gene may play a key role in the initial infection control of the human body, by promoting and maintaining the immune response of adaptive T cells.
锌是人体内仅次于铁的最常见微量元素。在生物体内，锌转运蛋白有助于锌从细胞内流入和流出。先前的研究报道，当细胞内的锌被 TPEN 耗尽时，人类单核细胞 THP-1 细胞中的 Zip2 上调了 27 倍以上。我们的研究发现，在哮喘婴儿的白细胞中，Zip2 过度表达，特别是在血清锌水平低于健康婴儿的婴儿中。肺结核（PTB）患者的血清锌水平显著降低。在这里，我们研究了 Zip2 水平是否在 PTB 患者中发生变化。通过定量实时 PCR 和 Western blot 分别检测来自 PTB（n1=23）和健康对照（n2=42）的外周血单个核细胞（PBMC）中的 Zip2 mRNA 和蛋白质水平。通过定量实时 PCR 检测了另外四种锌转运蛋白 Zip1、Zip6、Zip8 和 ZnT1 的 mRNA 表达水平。PTB 患者的 Zip2 mRNA 水平显著上调（P=0.001），与对照个体相比，Zip8 mRNA 水平显著下调（P<0.001）。相比之下，两组中 Zip1、Zip6 和 ZnT1 的 mRNA 水平均无显著变化（P>0.05）。与对照组相比，PTB 患者的 Zip2 蛋白表达水平增加。我们的研究发现，用 siRNA 敲低 ZIP2 会导致 PTB 患者 PBMC 中的 Zip2 水平降低，同时降低 INF-γ 的表达（P<0.01）并增加 IL-6 的表达（P<0.01）。这些数据表明，Zip2 基因的高表达与 PTB 患者的免疫密切相关，表明 Zip2 基因可能在人体对初始感染的控制中发挥关键作用，通过促进和维持适应性 T 细胞的免疫反应。
