Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1.
Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1.
复制标题
铁降低 RAW264.7 巨噬细胞中与 STAT1 抑制相关的 M1 巨噬细胞极化
DOI：
10.1155/2017/8570818
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发表时间：
2017
影响因子：
4.6
通讯作者：
Du HH
中科院分区：
文献类型：
--
作者：
Gan ZS;Wang QQ;Li JH;Wang XL;Wang YZ;Du HH
炎症中的铁代谢主要以暴露于病原体或炎症条件的巨噬细胞为特征。本研究的目的是探讨M1巨噬细胞极化和铁代谢之间的交叉调节相互作用。首先，我们研究了IFN-γ刺激下M1 RAW264.7巨噬细胞铁稳态相关基因的转录。M1巨噬细胞的分子特征显示出高水平的铁储存（铁蛋白），低水平的铁输出（ferroportin），以及铁调节剂（铁调素和转铁蛋白受体）的变化，这有利于网状内皮系统中的铁螯合，并有利于炎症性疾病。然后，我们评估了铁对M1巨噬细胞极化的影响。铁显著降低IFN-γ极化的M1巨噬细胞产生的IL-6、IL-1β、TNF-α和iNOS的mRNA水平。免疫荧光分析表明，铁也减少了iNOS的生产。然而，铁没有妥协，但增强了M1极化的巨噬细胞吞噬FITC-葡聚糖的能力。此外，我们证明，STAT 1抑制所需的iNOS和M1相关的细胞因子的生产减少铁的存在。总之，这些发现表明铁降低了M1巨噬细胞的极化，并抑制了促炎细胞因子的产生。结果扩展了我们对铁在巨噬细胞极化中的作用的认识。
Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN-γ. The molecular signature of M1 macrophages showed high levels of iron storage (ferritin), a low level of iron export (ferroportin), and changes of iron regulators (hepcidin and transferrin receptors), which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders. Then, we evaluated the effect of iron on M1 macrophage polarization. Iron significantly reduced mRNA levels of IL-6, IL-1β, TNF-α, and iNOS produced by IFN-γ-polarized M1 macrophages. Immunofluorescence analysis showed that iron also reduced iNOS production. However, iron did not compromise but enhanced the ability of M1-polarized macrophages to phagocytose FITC-dextran. Moreover, we demonstrated that STAT1 inhibition was required for reduction of iNOS and M1-related cytokines production by the present of iron. Together, these findings indicated that iron decreased polarization of M1 macrophages and inhibited the production of the proinflammatory cytokines. The results expanded our knowledge about the role of iron in macrophage polarization.