Jung Myunghwan, Shin Min-Kyoung, Jung Yeon-Kwon, Yoo Han Sang
Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Seobong BioBesstech Co., Ltd., Yeoksam-dong, Kangnam-gu, Seoul, Republic of Korea.
PLoS One. 2015 Feb 10;10(2):e0117838. doi: 10.1371/journal.pone.0117838. eCollection 2015.
It was reported that the aluminosilicate material mica activated macrophages and showed its immunostimulating effects. However, the mechanisms by which it exerts these effects are unclear. To address this, we evaluated the effects of mica fine particles (MFP, 804.1 ± 0.02 nm) on the murine macrophage cell line, RAW 264.7. Specifically, RAW 264.7 cells were treated with 100 and 500 μg/mL MFP and their proliferative response was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Changes in global gene expression upon MFP treatment for 12 and 48 h were also determined using microarrays. Following the MFP treatment, RAW 264.7 cells showed a low level of proliferation compared to nontreated cells (p < 0.01). There was a change in an expression level of 1,128 genes after 48 h treatment. Specifically, genes associated with the cell cycle, DNA replication, and pyrimidine and purine metabolisms, were down-regulated in cells treated with MFP, which resulted in reduction of cell proliferation. MFP treatment also up-regulated genes associated with lysosome and phagosome function, which are both required for macrophage activities. We speculate that activation of macrophages by mica is in part derived from up-regulation of these pathways.
据报道,铝硅酸盐材料云母可激活巨噬细胞并显示出其免疫刺激作用。然而,其发挥这些作用的机制尚不清楚。为了解决这个问题,我们评估了云母细颗粒(MFP,804.1±0.02纳米)对小鼠巨噬细胞系RAW 264.7的影响。具体而言,用100和500μg/mL的MFP处理RAW 264.7细胞,并使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法测定其增殖反应。还使用微阵列确定了MFP处理12和48小时后全局基因表达的变化。MFP处理后,RAW 264.7细胞与未处理的细胞相比显示出低水平的增殖(p<0.01)。48小时处理后1128个基因的表达水平发生了变化。具体而言,在用MFP处理的细胞中,与细胞周期、DNA复制以及嘧啶和嘌呤代谢相关的基因被下调,这导致细胞增殖减少。MFP处理还上调了与溶酶体和吞噬体功能相关的基因,而这两者都是巨噬细胞活动所必需的。我们推测云母对巨噬细胞的激活部分源于这些途径的上调。