STEAROYL LYSOPHOSPHATIDYLCHOLINE INHIBITS ENDOTOXIN-INDUCED CASPASE-11 ACTIVATION

被引：29
作者：
Li, Wenbo [1 ,2 ]
Zhang, Wei [3 ,6 ]
Deng, Meihong [2 ]
Loughran, Patricia [5 ]
Tang, Yiting [4 ]
Liao, Hong [2 ]
Zhang, Xianying [7 ,8 ]
Liu, Jian [7 ,8 ]
Billiar, Timothy R. [1 ,2 ]
Lu, Ben [4 ,7 ,8 ]
机构：
[1] Cent South Univ, Xiangya Hosp 3, Dept Surg, Changsha, Hunan, Peoples R China
[2] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA
[3] Hunan Inst Drug Control, Changsha, Hunan, Peoples R China
[4] Cent South Univ, State Key Lab Med Genet, Sch Biol Sci & Technol, Changsha, Hunan, Peoples R China
[5] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA USA
[6] Cent South Univ, Sch Pharmaceut Sci, Changsha, Hunan, Peoples R China
[7] Cent South Univ, Dept Hematol, Xiangya Hosp 3, Changsha, Hunan, Peoples R China
[8] Cent South Univ, Inst Infect & Computat Med, Xiangya Hosp 3, Changsha, Hunan, Peoples R China
来源：
SHOCK | 2018年 / 50卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Innate immunity; non-canonical inflammasome; endotoxemia; pyroptosis; NONCANONICAL INFLAMMASOME ACTIVATION; LPS; ATHEROSCLEROSIS; REQUIRES; RELEASE; SEPSIS;
D O I：
10.1097/SHK.0000000000001012
中图分类号：
R4 [临床医学];
学科分类号：
1002 ; 100602 ;
摘要：
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-11mediated 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 caspase11. Moreover, stearoyl LPC treatment conferred significant protection against lethal endotoxemia and significantly reduced the release of IL-1 alpha and IL-1 beta. 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.
引用
收藏
页码：339 / 345
页数：7
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