High salt primes a specific activation state of macrophages, M(Na).
High salt primes a specific activation state of macrophages, M(Na).
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高盐会引发巨噬细胞的特定激活状态 M(Na)。
DOI：
10.1038/cr.2015.87
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发表时间：
2015-08
期刊：
影响因子：
44.1
通讯作者：
Duan SZ
中科院分区：
文献类型：
--
作者：
Zhang WC;Zheng XJ;Du LJ;Sun JY;Shen ZX;Shi C;Sun S;Zhang Z;Chen XQ;Qin M;Liu X;Tao J;Jia L;Fan HY;Zhou B;Yu Y;Ying H;Hui L;Liu X;Yi X;Liu X;Zhang L;Duan SZ
高盐与许多疾病的风险呈正相关。然而，人们对其机制知之甚少。本研究表明，在人和小鼠巨噬细胞中，高盐增加了促炎分子，而减少了抗炎和前吞分子。高盐还能增强脂多糖诱导的巨噬细胞活化，抑制白细胞介素4诱导的巨噬细胞活化。高盐通过激活p38/cFos和/或Erk1/2/cFos通路诱导促炎，而通过Erk1/2/信号转导和转录激活因子6通路抑制抗炎和前吞作用。与体外实验结果一致，高盐饮食增加了小鼠肺泡巨噬细胞的促炎基因表达。在小鼠急性肺损伤模型中，高盐饮食加重了脂多糖诱导的肺巨噬细胞活化和肺部炎症。这些结果确定了一种新的巨噬细胞激活状态M（Na）和高盐是通过诱导M（Na）引起肺部炎症的潜在环境危险因素。
High salt is positively associated with the risk of many diseases. However, little is known about the mechanisms. Here we showed that high salt increased proinflammatory molecules, while decreased anti-inflammatory and proendocytic molecules in both human and mouse macrophages. High salt also potentiated lipopolysaccharide-induced macrophage activation and suppressed interleukin 4-induced macrophage activation. High salt induced the proinflammatory aspects by activating p38/cFos and/or Erk1/2/cFos pathways, while inhibited the anti-inflammatory and proendocytic aspects by Erk1/2/signal transducer and activator of transcription 6 pathway. Consistent with the in vitro results, high-salt diet increased proinflammatory gene expression of mouse alveolar macrophages. In mouse models of acute lung injury, high-salt diet aggravated lipopolysaccharide-induced pulmonary macrophage activation and inflammation in lungs. These results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na).