High salt primes a specific activation state of macrophages, M(Na)

Wu-Chang Zhang1,*, Xiao-Jun Zheng1,*, Lin-Juan Du1,*, Jian-Yong Sun1, Zhu-Xia Shen1, Chaoji Shi2, Shuyang Sun2, Zhiyuan Zhang2, Xiao-qing Chen3, Mu Qin3, Xu Liu3, Jun Tao4, Lijun Jia5, Heng-yu Fan6, Bin Zhou1, Ying Yu1, Hao Ying1, Lijian Hui7, Xiaolong Liu7, Xianghua Yi8, Xiaojing Liu9, Lanjing Zhang10,11,12,13 and Sheng-Zhong Duan1

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).

http://www.nature.com/cr/journal/v25/n8/full/cr201587a.html