| Project/Area Number |
17390562
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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 |
Periodontal dentistry
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| Research Institution | Hiroshima University (2006-2007)
Okayama University (2005) |
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Principal Investigator |
NISHIMURA Fusanori Hiroshima University, Graduate School of Biomedical Sciences, Professor (80208222)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Hiroshi Okayama University, Hospital, Lecturer (00274001)
IWAMOTO Yoshihiro Okayama University, Hospital, Assistant Professor (80362979)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,190,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥690,000)
Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2006: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | periodontal inflammation / low-grade inflammation / hepatocyte / adipose tissue / cytokine / hyperglycemia / JNK / HMG-CoA reductase / マクロファージ / TLR-4 / LPS / 脂肪細胞-マクロファージ相互作用 / インスリン抵抗性 / 歯周病 / 虚血性心疾患 / 高感度CRP / アディポサイトカイン / IL-6 / TNF-α / マクロファージー / 脂肪細胞 / 動脈硬化 / 慢性炎症 / 高コレステロール血症 / Porphyromonas gingivalis / HMG-CoA還元酵素 / 肝細胞 / インターロイキン-6 |
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| Research Abstract |
Local periodontal inflammation is amplified to influence insulin resistance and to promote vascular disorders. To explain the underlying mechanisms as to how local periodontal infection is amplified to such level, we hypothesized that inflammation could be evoked in the liver by periodontal infection, and elucidated following points
1. Diabetic subjects with high antibody titer to periodontal bacteria exhibited significantly higher level of total and LDL-cholesterol as compared with diabetic subjects with low antibody titer.
2. Lipopelysaccharide did not influence HMG-CoA reductase gene expression in cultured hepatocelkilar carcinoma cell line, Hep G2. However, both IL-6 and TNF-α, at physiological concentration, up-regulated HMG-CoA reductase gene expression. Therefore, inflammation appeared to up-regulate cholesterol synthesis in the liver.
3. We established co-culture system between adipocyte and macrophage. When we stimulated co-cultures with LPS, IL-6 and MCP-1 production markedly increased.
4. Macrophages under hyperglycemic condition produced higher amounts of MCP-1 and TNF-α via JNK pathway as compared with the cells under normal glucose concentration. Based on these observations, we concluded that activated macrophages by periodontal infection accumulate in adipose tissue and interact with adipocytes, and that these cells produce enhanced amounts of MCP-1 and IL-6. MCP-1 further act to recruit macrophages into adipose tissue, and IL-6 enters in the liver via portal vein and acts as a key mediator to evoke liver inflammation.
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