Stearoyl lysophosphatidylcholine prevents lipopolysaccharide-induced extracellular release of high mobility group box-1 through AMP-activated protein kinase activation

• Published in: International immunopharmacology 2015-09, Vol.28 (1), p.540-545
• Main Authors: Kim, Joung-Min, Han, Hui-Jing, Hur, Young-Hoe, Quan, Hui, Kwak, Sang-Hyun, Choi, Jeong-Il, Bae, Hong-Beom
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - metabolism; AMP-Activated Protein Kinases - metabolism; Animals; Bronchoalveolar Lavage Fluid - chemistry; Cell Line; Cell Survival - drug effects; HMGB1; HMGB1 Protein - metabolism; Lipopolysaccharides; LPS; Lung - drug effects; Lung - metabolism; Lysophosphatidylcholines - pharmacology; Macrophage; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Male; Mice, Inbred BALB C; Stearoyl lysophosphatidylcholine
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2015.07.010

Previous studies have suggested that stearoyl lysophosphatidlycholine (LPC) protects against lethal experimental sepsis by inhibiting lipopolysaccharide (LPS)-induced extracellular release of high-mobility group box 1 (HMGB1). However, limited information exists on the mechanism by which stearoyl-LPC suppresses the extracellular release of HMGB1 in monocyte/macrophages stimulated with LPS. In this study, we found that stearoyl-LPC increased the phosphorylation of AMP-activated protein kinase (AMPK) in macrophages. Exposure of LPS-stimulated macrophages to stearoyl-LPC decreased the extracellular release of HMGB1 in peritoneal macrophages, which were inhibited by the AMPK inhibitor, compound C. In addition, stearoyl-LPC-mediated suppression of HMGB1 release was abolished by siRNA-mediated knock-down of AMPKα1. Stearoyl-LPC increased the phosphorylation of acetyl-CoA carboxylase (ACC), a downstream target of activated AMPK, in mice lungs and decreased HMGB1 levels in bronchoalveolar lavage fluids in mice administered LPS. These results reveal a novel mechanism by which stearoyl-LPC regulates LPS-mediated cellular translocation of HMGB1. •Stearoyl-LPC increases the phosphorylation of AMPK and ACC in macrophages.•Stearoyl-LPC decreases extracellular release of HMGB1 in LPS-stimulated macrophages.•Inhibition of AMPK activity abolishes the effect of stearoyl-LPC on LPS-induced extracellular release of HMGB1.•Stearoyl-LPC decreased the concentration of HMGB1 in BAL fluid in LPS-injured lung.