Identification of lipopolysaccharide-binding peptide regions within HMGB1 and their effects on subclinical endotoxemia in a mouse modelopen access
- Authors
- Youn, Ju Ho; Kwak, Man Sup; Wu, Jie; Kim, Eun Sook; Ji, Yeounjung; Min, Hyun Jin; Yoo, Ji-Ho; Choi, Ji Eun; Cho, Hyun-Soo; Shin, Jeon-Soo
- Issue Date
- Sep-2011
- Publisher
- WILEY-BLACKWELL
- Keywords
- Endotoxin shock; High mobility group box 1; Inflammation; Lipopolysaccharide
- Citation
- EUROPEAN JOURNAL OF IMMUNOLOGY, v.41, no.9, pp 2753 - 2762
- Pages
- 10
- Journal Title
- EUROPEAN JOURNAL OF IMMUNOLOGY
- Volume
- 41
- Number
- 9
- Start Page
- 2753
- End Page
- 2762
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/46367
- DOI
- 10.1002/eji.201141391
- ISSN
- 0014-2980
1521-4141
- 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-alpha 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-alpha release in human PBMCs and induced lower levels of TNF-alpha 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.
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