• Wenbo Li, Wei Zhang, Meihong Deng, Patricia Loughran, Yiting Tang, Hong Liao, Xianying Zhang, Jian Liu, Timothy R Billiar, and Ben Lu.
• Department of Surgery, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.
• Shock. 2018 Sep 1; 50 (3): 339-345.

AbstractStearoyl 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-11-mediated 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 caspase-11. Moreover, stearoyl LPC treatment conferred significant protection against lethal endotoxemia and significantly reduced the release of IL-1α and IL-1β. 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.

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