2007 Fiscal Year Final Research Report Summary
Evaluation of biological activity of the glycolipids by device cultured cells
| Project/Area Number |
17550163
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemistry related to living body
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
FUKUOKA Satoshi National Institute of Advanced Industrial Science and Technology, National Institute of Advanced Industrial Science and Technology, Health Technology Research Center, Senior Researcher (40357885)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Cell / Biological activity / cytokine / Lipopolysaccharide / Lipid A |
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| Research Abstract |
The device cultured cells were applied for biological activity evaluation of glycoconjugates, polysaccharides, and other materials. Lipid A from bacterial lipopolysaccharide(LPS) was used as a model compound that is a biological active center of LPS which located on the outer membrane of Gram-negative bacteria. As a biological activity, cytokine(tumor necrosis factor, TNF-α) production by cultured cells was studied. Homogeneous lipid A samples were isolated and purified from LPS of Erwinia carotovora. In addition, preparation of highly sensitive probe for cell evaluation and study for signal transduction by lipid A was performed. The molecular level interaction of lipid A with antimicrobial peptides was investigated to elucidate the expression mechanisms and deactivation methods. The lipid A induced cytokine production in mononuclear cells showed that the ability of the two peptides to inhibit a TNF-α production correlates with characteristic changes of the biophysical parameters as phase transition, molecular arrangement, etc. These are much stronger expressed for the modified peptide, which apparently is connected with the higher number of positive as well as more hydrophobic amino acids, leading to a stronger amphiphilicity necessary to neutralize the amphiphilic lipid A aggregates. By this study, molecular level mechanism of biological activity for lipid A was introduced. This will lead to the remedy of sepsis and other syndromes introduced by bacterial infection.
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