| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Yoshikazu Meikai University, School of dentistry, Associate Professor, 歯学部, 准教授 (90206219)
TAKESHITA Akira Meikai University, School of dentistry, Associate Professor, 歯学部, 准教授 (70236454)
MATSUMOTO Masaru Meikai University, School of dentistry, Associate Professor, 歯学部, 准教授 (00209652)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Oral malodor is caused by volatile sulfur compounds (VSCs) including methylmercapton. Several studies showed that amount of methylmercapton are correlated with deeper pockets. In addition, resent studies show that periodontopathic bacteria produce the VSC. Therefore, it is proposed us that methylmercaptan plays a functional role (s) as pathogen factor for induction and progression of periodontal disease.
Resent studies have investigated that many dead epithelial cells are detected in the area of deeper or bleeding pockets. However, it is not known the cytotoxic mechanisms of the cells, completely. And so, we examine a possibility that methylmercapton induces the cell death via using oral epithelial cell line KB cells and observed that the VSC exhibits cytotoxic effect on KB cells via necrosis manner.
Periodontal disease is a chronic disease characterized by inflammation of gingival and resorption of alveolar bone in periodontal tissues. Resent studies indicated that virulence factors of
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pathogenic bacteria, such as lipopolysacchaaride (LPS), are able to stimulate inflammatory cytokines (IL-1, TNF-alpha, and IL-6), which are also inducers of bone resorption, and then, these cytokines closely contribute to progression of periodontal disease. It has been showed that hight mobility group protein 1 (HMGB1), an architectural chromatin-binding factor, is released from necrotic cells but not apoptotic cells and that HMGB1 is able to stimulate expression of IL-1 and TNF-alpha in monocyte and macrophage. Then, it has been suggested that HMGB1 is a DNA binding cytokine and also promote necrosis-induced inflammation. It is interesting to demonstrate that HMGB1 is secreted from necrotic KB cells destroyed by methylmercapton, and we examined whether the supernatant of the death cells is able to induce expression of TNF-alpha in mouse macrophage like cell line RAW264.7 cells. Then the supernatant stimulated the expression of TNF-alpha and the biological activity was abolished by treatment of anti-HMGB1 antibody.
Therefore, it was suggested a possibility that methylmercapton induces the necrosis of oral epithelial cell and the necrosis is able to stimulate the expression of inflammation cytokines through the release of HMGB1 from the necrosis cells, in adult periodontal disease. Less
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