Interaction between Bacterial Endotoxin and Lysozyme
| Project/Area Number |
07457448
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | Kyushu University |
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Principal Investigator |
ITO Hiro-O (1996) Kyushu Univ., Dent., Research Fellow, 歯学部, 助手 (40213079)
古賀 敏生 (1995) 九州大学, 歯学部, 教授 (00037540)
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| Co-Investigator(Kenkyū-buntansha) |
IMOTO Taiji Kyushu Univ., Pharm. Sci., Professor, 薬学部, 教授 (90038282)
HIRATA Masato Kyushu Univ., Dent., Professor, 歯学部, 教授 (60136471)
伊藤 博夫 九州大学, 歯学部, 助手 (40213079)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | Lysozyme (Muramidase) / Lipopolysaccharide (Endotoxin) / Lipid A / Periodontitis (Periodontal Disease) / Osteoclasts / Immunopharmacology / 腫瘍壊死因子 / マイトゲン / 多クローン性B細胞活性化 |
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| Research Abstract |
Bacterial endotoxin (lipopolysaccharide ; LPS) is a cell-surface substance of gram-negative bacteria, and considered to be an important pethogenic factor for human inflammatory periodontitis. Lysozyme has a bactericidal activity for gram-positive bacteria, by enzymatic cleavage of peptidoglycans that constitute the cell wall. It has also been reported that lysozyme binds to LPS and inhibits the immunopharmacological activities. In this study, we showed that LPS purified from three putative periodontopathic bacteria (Prevotella intermedia, Actinbacillus actinomycetemcomitans, Porphyromonas gingivalis) as well as LPS from Escherichia coli promote osteoclast formation in mouse bone marrow cell cultures. This activity of LPS was attenuated by hen egg-white lysozyme (HEL). Other various biological activities of LPS,i.e. activation of Limulus amoebocyte lysate. stimulation of human leukocytes to secrete TNF-alpha, polyclonal activation of mouse B cells, were inhibited by HEL.The bioactivitiy of synthetic lipid A was also inhibited by HEL,suggesting that HEL reacts to the common lipid A portion of LPS.Various chemically nodified HEL were produced and tested for their ability to inhibit the LPS activities. Among those HEL-derivatives, S-trimethylammonium-propylated HEL,the derivative designed to posses higher water solubility and higher pI,most efficiently inhibit LPS activities. The anti-endotoxic capacity of HEL was not related to its known enzymatic activity as a muramidase. These results suggest a possible application of HEL to the periodontal therapy as an anti-endotoxic agent, and the potential of protein engineering to denerate a novel drug that efficiently neutralize endotoxin.
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Report
(3 results)
Research Products
(8 results)
