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

Cell Res. 2015 Aug;25(8):893-910. doi: 10.1038/cr.2015.87. Epub 2015 Jul 24.


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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / metabolism
  • Acute Lung Injury / physiopathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Humans
  • Inflammation
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System
  • Macrophage Activation* / drug effects
  • Macrophage Activation* / physiology
  • Macrophages / drug effects*
  • Macrophages / physiology
  • Mice
  • Sodium Chloride / adverse effects*


  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Sodium Chloride