title: 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Joung-Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hui-Jing
authors.initials: HJ
authors.lastname: Han
authors.affiliation: Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Young-Hoe
authors.initials: YH
authors.lastname: Hur
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Quan
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kwak
authors.affiliation: 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.
authors.forename: Jeong-Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Hong-Beom
authors.initials: HB
authors.lastname: Bae
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D055372:AMP-Activated Protein Kinases
keywords: HMGB1; LPS; Macrophage; Stearoyl lysophosphatidylcholine