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Stearoyl Lysophosphatidylcholine Inhibits Endotoxin-Induced Caspase-11 Activation

Li, Wenbo*,†; Zhang, Wei‡,§; Deng, Meihong; Loughran, Patricia; Tang, Yiting||; Liao, Hong; Zhang, Xianying**; Liu, Jian**; Billiar, Timothy R.*,†; Lu, Ben||,**

doi: 10.1097/SHK.0000000000001012
Basic Science Aspects
Editor's Choice

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-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.

*Department of Surgery, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania

Hunan Institute for Drug Control, Changsha, Hunan, China

||State Key Laboratory of Medical Genetics, School of Biological Science and Technology, Central South University, Changsha, Hunan, China

Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania

§School of Pharmaceutical Sciences of Central South University, Changsha, Hunan, China

**Department of Hematology and Institute of Infection & Computational Medicine, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China

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

Received 17 May, 2017

Revised 7 June, 2017

Accepted 25 September, 2017

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.

© 2018 by the Shock Society