@article{1ff61c1962c54295842ed87ec62d5f7e,
title = "Stearoyl lysophosphatidylcholine inhibits endotoxin-induced caspase-11 activation",
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-1a 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.",
keywords = "Endotoxemia, Innate immunity, Non-canonical inflammasome, Pyroptosis",
author = "Wenbo Li and Wei Zhang and Meihong Deng and Patricia Loughran and Yiting Tang and Hong Liao and Xianying Zhang and Jian Liu and Billiar, {Timothy R.} and Ben Lu",
note = "Funding Information: Mouse peritoneal macrophages were isolated and cultured as described (14). Briefly, C57BL/6 mice (8–10 weeks old) were injected intraperitoneally with 2 mL of sterile 4% thioglycollate broth to elicit peritoneal macrophages. At 48– 72 h later, cells were collected by lavage of the peritoneal cavity with 5 mL of sterile 11.6% sucrose. Harvested cells were washed, then re-suspended in RPMI 1640 medium (Gibco) supplemented with 10% heat-inactivated fetal bovine serum (FBS) and antibiotics (Gibco). Peritoneal macrophages were plated in 12-well plates (106/well) and primed for 6 h with ultra-pure LPS (100 ng/mL) or Pam3CSK4 (1 µg/mL). Primed cells were washed with phosphate-buffered Address reprint requests to Ben Lu, PhD, MD, 138 Yuelu Road, Changsha, Hunan 410013, China. E-mail: xybenlu@csu.edu.cn; Timothy R. Billiar, MD, 200 Lothrop Street, Pittsburgh, PA 15213. E-mail: billiartr@upmc.edu This work was supported by National key scientific project (no. 2015CB910700) (to BL), National Natural Science Foundation of China (nos. 81422027 and 81470345 (to BL) and no. 81571879 (to TRB) and NIH grant RO1 GM50441 (to TRB). The authors declare no conflicts of interest. DOI: 10.1097/SHK.0000000000001012 Copyright {\textcopyright} 2017 by the Shock Society saline (PBS) and treated for 2 h with stearoyl LPC, which had been prepared as before (13). Cells were washed again with PBS and treated with the combination of LPS (1 µg/mL) and a mixture of cholera toxin subunit B (CTB, 20 µg/ mL) or Dotap, which had been prepared by mixing CTB and Dotap in Optim (Gibco) for 20 min at room temperature. At 16 h after treatment, cells were harvested and total lysates were prepared for analysis using Western blotting an assay for lactate dehydrogenase (LDH). In some experiments, macrophages were treated with LPC without priming. In other experiments, macrophages were treated with anti-G2A antibody (1 µg/mL) alone or with the combination of LPC and anti-G2A antibody (1 µg/mL). Publisher Copyright: Copyright {\textcopyright} 2017 by the Shock Society.",
year = "2018",
doi = "10.1097/SHK.0000000000001012",
language = "English",
volume = "50",
pages = "339--345",
journal = "Shock",
issn = "1073-2322",
number = "3",
}