title: Anti-septic effects of glyceollins in HMGB1-induced inflammatory responses in vitro and in vivo.
abstract: The ubiquitous nuclear protein High mobility group box 1 (HMGB1) is released by activated macrophages and human umbilical vein endothelial cells (HUVECs), and functions as a late mediator of experimental sepsis. Glyceollins (GCLs) are active compounds from Aspergillus sojae which have been reported for anti-cancer, anti-diabetes, and anti-inflammatory activities. We investigated here, the antiseptic effects and underlying mechanisms of GCLs against HMGB1-mediated septic responses in HUVECs and mice. According to the results, GCLs effectively inhibited lipopolysaccharide-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, GCLs suppressed the production of tumor necrosis factor-α and interleukin 6 and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate that GCLs could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: You-Mie
authors.initials: YM
authors.lastname: Lee
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: baejs@knu.ac.kr.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024243:HMGB1 Protein / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D036343:Pterocarpans / Q000494:pharmacology / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D024243:HMGB1 Protein; D036343:Pterocarpans; C017343:glyceollin
keywords: Glyceollins; HMGB1; Inflammation; Sepsis