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Shock. 2018 Sep;50(3):339-345. doi: 10.1097/SHK.0000000000001012.

Stearoyl Lysophosphatidylcholine Inhibits Endotoxin-Induced Caspase-11 Activation.

Author information

1
Department of Surgery, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.
2
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
3
Hunan Institute for Drug Control, Changsha, Hunan, China.
4
School of Pharmaceutical Sciences of Central South University, Changsha, Hunan, China.
5
Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania.
6
State Key Laboratory of Medical Genetics, School of Biological Science and Technology, Central South University, Changsha, Hunan, China.
7
Department of Hematology and Institute of Infection & Computational Medicine, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

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-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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