Stearoyl Lysophosphatidylcholine Inhibits Endotoxin-Induced Caspase-11 Activation

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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 LPS plus CTB 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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