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Identification of lipopolysaccharide-binding peptide regions within HMGB1 and their effects on subclinical endotoxemia in a mouse model.

Title
Identification of lipopolysaccharide-binding peptide regions within HMGB1 and their effects on subclinical endotoxemia in a mouse model.
Authors
Ju Ho Youn;Man Sup Kwak;Jeon-Soo Shin;Hyun-Soo Cho;Ji Eun Choi;Ji-Ho Yoo;Hyun Jin Min;Yeounjung Ji;Eun Sook Kim;Jie Wu
Issue Date
2011
Journal Title
European Journal of Immunology
ISSN
0014-2980
Citation
European Journal of Immunology, Vol.41(9) : 2753~2762, 2011
Abstract
Lipopolysaccharide (LPS) triggers deleterious systemic inflammatory responses when released into the circulation. LPS-binding protein (LBP) in the serum plays an important role in modifying LPS toxicity by facilitating its interaction with LPS signaling receptors, which are expressed on the surface of LPS-responsive cells. We have previously demonstrated that high mobility group box 1 (HMGB1) can bind to and transfer LPS, consequently increasing LPS-induced TNF-α production in human peripheral blood mononuclear cells (PBMCs). We report here on the identification of two LPS-binding domains within HMGB1. Furthermore, using 12 synthetic HMGB1 peptides, we define the LPS-binding regions within each domain. Among them, synthetic peptides HPep1 and HPep6, which are located in the A and B box domains of HMGB1, bind to the polysaccharide and lipid A moieties of LPS respectively. Both HPep1 and HPep6 peptides inhibited binding of LPS to LBP and HMGB1, LBP-mediated LPS transfer to CD14, and cellular uptake of LPS in RAW264.7 cells. These peptides also inhibited LPS-induced TNF-α release in human PBMCs and induced lower levels of TNF-α in the serum in a subclinical endotoxemia mouse model. These results indicate that HMGB1 has two LPS-binding peptide regions that can be utilized to design anti-sepsis or LPS-neutralizing therapeutics
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/93615
DOI
10.1002/eji.201141391
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Microbiology
Yonsei Authors
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