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Int Immunopharmacol. 2015 Sep;28(1):540-5. doi: 10.1016/j.intimp.2015.07.010. Epub 2015 Jul 25.

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

Author information

1
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
2
Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea.
3
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea; The Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, Republic of Korea.
4
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea; The Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, Republic of Korea. Electronic address: nextphil2@jnu.ac.kr.

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.

KEYWORDS:

HMGB1; LPS; Macrophage; Stearoyl lysophosphatidylcholine

PMID:
26218280
DOI:
10.1016/j.intimp.2015.07.010
[Indexed for MEDLINE]

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