Stearoyl Lysophosphatidylcholine Inhibits Endotoxin-Induced Caspase-11 Activation

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspases / metabolism*
  • Caspases, Initiator
  • Endotoxemia / metabolism
  • Endotoxemia / pathology
  • Enzyme Activation / drug effects
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / toxicity*
  • Lysophosphatidylcholines / pharmacology*
  • Macrophages, Peritoneal / metabolism*
  • Macrophages, Peritoneal / pathology
  • Mice


  • IL1B protein, mouse
  • Interleukin-1alpha
  • Interleukin-1beta
  • Lipopolysaccharides
  • Lysophosphatidylcholines
  • stearoyl alpha-lysolecithin
  • Casp4 protein, mouse
  • Caspases
  • Caspases, Initiator