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Stearoyl lysophosphatidylcholine prevents lipopolysaccharide-induced extracellular release of high mobility group box-1 through AMP-activated protein kinase activation.

Abstract：

:Previous studies have suggested that stearoyl lysophosphatidlycholine (LPC) protects against lethal experimental sepsis by inhibiting lipopolysaccharide (LPS)-induced extracellular release of high-mobility group box 1 (HMGB1). However, limited information exists on the mechanism by which stearoyl-LPC suppresses the extracellular release of HMGB1 in monocyte/macrophages stimulated with LPS. In this study, we found that stearoyl-LPC increased the phosphorylation of AMP-activated protein kinase (AMPK) in macrophages. Exposure of LPS-stimulated macrophages to stearoyl-LPC decreased the extracellular release of HMGB1 in peritoneal macrophages, which were inhibited by the AMPK inhibitor, compound C. In addition, stearoyl-LPC-mediated suppression of HMGB1 release was abolished by siRNA-mediated knock-down of AMPKα1. Stearoyl-LPC increased the phosphorylation of acetyl-CoA carboxylase (ACC), a downstream target of activated AMPK, in mice lungs and decreased HMGB1 levels in bronchoalveolar lavage fluids in mice administered LPS. These results reveal a novel mechanism by which stearoyl-LPC regulates LPS-mediated cellular translocation of HMGB1.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Kim JM,Han HJ,Hur YH,Quan H,Kwak SH,Choi JI,Bae HB

doi

10.1016/j.intimp.2015.07.010

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

540-5

issue

1

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(15)30023-0

journal_volume

28

pub_type

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