STEAROYL LYSOPHOSPHATIDYLCHOLINE INHIBITS ENDOTOXIN-INDUCED CASPASE-11 ACTIVATION

作者：Li, Wenbo; Zhang, Wei; Deng, Meihong; Loughran, Patricia; Tang, Yiting; Liao, Hong; Zhang, Xianying; Liu, Jian; Billiar, Timothy R.^*; Lu, Ben^*

来源：Shock, 2018, 50(3): 339-345.

DOI：10.1097/SHK.0000000000001012

• Innate immunity
• non-canonical inflammasome
• endotoxemia
• pyroptosis

Stearoyl lysophosphatidylcholine (LPC) exerts protective effect during endotoxemia and in experimental sepsis, but the underlying mechanism is unclear. Here, we demonstrated that stearoyl LPC could block caspase-11mediated macrophage pyroptosis. In vitro, stearoyl LPC significantly decreased caspase-11 activation and pyroptosis induced by lipopolysaccharide (LPS) plus cholera toxin subunit B independent of the receptor G2A. Stearoyl LPC did not affect LPS uptake by mouse peritoneal macrophages but did significantly inhibit the interaction between LPS and caspase11. Moreover, stearoyl LPC treatment conferred significant protection against lethal endotoxemia and significantly reduced the release of IL-1 alpha and IL-1 beta. These findings identify stearoyl LPC as an inhibitor of LPS-mediated caspase-11 activation. This mechanism could explain the protective action of stearoyl LPC in experimental sepsis and endotoxemia.

• 出版日期2018-9
• 单位湖南省药品检验所; 中南大学