STEAROYL LYSOPHOSPHATIDYLCHOLINE INHIBITS ENDOTOXIN- INDUCED CASPASE-11
STEAROYL LYSOPHOSPHATIDYLCHOLINE INHIBITS ENDOTOXIN- INDUCED CASPASE-11
复制标题
硬脂酰溶血磷脂酰胆碱抑制内毒素诱导的 CASPASE-11
作者：
李文波;Timothy R.Billiar;吕奔
硬脂酰溶血磷脂酰胆碱（LPC）在内毒素血症和实验性脓毒症中发挥保护作用，但其机制尚不清楚。在这里，我们证明了硬脂酰LPC可以阻断caspase-11介导的巨噬细胞凋亡。在体外，硬脂酰LPC显着降低caspase-11激活和焦亡诱导的脂多糖（LPS）加霍乱毒素亚单位B的受体G2 A无关。硬脂酰LPC不影响小鼠腹腔巨噬细胞对LPS的摄取，但能显著抑制LPS与caspase- 11之间的相互作用。此外，硬脂酰LPC处理赋予了对致死性内毒素血症的显著保护，并显著减少了IL-1a和IL-1b的释放。这些发现确定硬脂酰LPC作为LPS介导的半胱天冬酶-11活化的抑制剂。这一机制可以解释硬脂酰LPC对实验性脓毒症和内毒素血症的保护作用。
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-1b. 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.