Source:http://linkedlifedata.com/resource/pubmed/id/18354232
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2008-3-20
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pubmed:abstractText |
LPS-binding protein (LBP) is a central mediator that transfers LPS to CD14 to initiate TLR4-mediated proinflammatory response. However, a possibility of another LPS transfer molecule has been suggested because LBP-deficient mice showed almost normal inflammatory response after LPS injection. In this study, we describe the novel finding that high mobility group box 1 protein (HMGB1) recently identified as a mediator of sepsis has a function of LPS transfer for a proinflammatory response. We used ELISA and surface plasmon resonance to show that HMGB1 binds LPS in a concentration-dependent manner and that the binding is stronger to lipid A moiety than to the polysaccharide moiety of LPS. This binding was inhibited by LBP and polymyxin B. Using native PAGE and fluorescence-based LPS transfer analyses, we show that HMGB1 can catalytically disaggregate and transfer LPS to both soluble CD14 protein and to human PBMCs in a dose-dependent manner. However, this effect was dramatically reduced to the baseline level when HMGB1 was heat inactivated. Furthermore, a mixture of HMGB1 and LPS treatment results in a higher increase in TNF-alpha production in human PBMCs and peripheral blood monocytes than LPS or HMGB1 treatment alone or their summation. Thus, we propose that HMGB1 plays an important role in Gram-negative sepsis by catalyzing movement of LPS monomers from LPS aggregates to CD14 to initiate a TLR4-mediated proinflammatory response.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD14,
http://linkedlifedata.com/resource/pubmed/chemical/HMGB1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Micelles,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
180
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5067-74
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pubmed:meshHeading |
pubmed-meshheading:18354232-Animals,
pubmed-meshheading:18354232-Antigens, CD14,
pubmed-meshheading:18354232-CHO Cells,
pubmed-meshheading:18354232-Catalysis,
pubmed-meshheading:18354232-Cricetinae,
pubmed-meshheading:18354232-Cricetulus,
pubmed-meshheading:18354232-HMGB1 Protein,
pubmed-meshheading:18354232-Humans,
pubmed-meshheading:18354232-Leukocytes,
pubmed-meshheading:18354232-Lipopolysaccharides,
pubmed-meshheading:18354232-Micelles,
pubmed-meshheading:18354232-Monocytes,
pubmed-meshheading:18354232-Protein Binding,
pubmed-meshheading:18354232-Solubility,
pubmed-meshheading:18354232-Surface Plasmon Resonance,
pubmed-meshheading:18354232-Tumor Necrosis Factor-alpha
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pubmed:year |
2008
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pubmed:articleTitle |
High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes.
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pubmed:affiliation |
Department of Microbiology, Brain Korea 21 Project for Medical Science, National Core Research Center for Nanomedical Technology, Yonsei University College of Medicine, Seoul, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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