M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells.
M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells.
复制标题
巨噬细胞的 M2 极化促进砷诱导的肺上皮细胞转化
DOI：
10.18632/oncotarget.15232
复制
发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Cui J;Xu W;Chen J;Li H;Dai L;Frank JA;Peng S;Wang S;Chen G
慢性砷暴露时微环境的改变可能导致砷诱导的肺癌发生。免疫细胞（例如巨噬细胞）在介导肺中的微环境中起着重要作用。激活后巨噬细胞执行其功能。巨噬细胞有两个激活状态：经典（M1）或替代性（M2）；后者与肿瘤发生有关。我们以前的工作表明，长期的砷暴露会诱导肺上皮细胞的转化。然而，尚未研究砷暴露后上皮细胞和巨噬细胞之间的串扰。在这项研究中，使用共培养系统，其中人类肺上皮细胞用巨噬细胞培养，我们确定长期的砷暴露会使巨噬细胞通过ROS产生偏向M2状态。与上皮细胞共培养进一步增强了巨噬细胞的极化以及上皮细胞的转化，而阻断巨噬细胞M2极化则降低了转化。此外，巨噬细胞M2极化降低了自噬活性，这可能是与巨噬细胞共培养的上皮细胞转化增加的。
The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with macrophages, we determined that long-term arsenic exposure polarizes macrophages towards M2 status through ROS generation. Co-culture with epithelial cells further enhanced the polarization of macrophages as well as transformation of epithelial cells, while blocking macrophage M2 polarization decreased the transformation. In addition, macrophage M2 polarization decreased autophagy activity, which may account for increased cell transformation of epithelial cells with co-culture of macrophages.