| Project/Area Number |
17390483
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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 |
Morphological basic dentistry
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAWARA Shunji Tohoku University, Graduate School of Dentistry, Professor, 大学院歯学研究科, 教授 (10241639)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Yasuo Tohoku University, Graduate School of Dentistry, Associate Professor, 大学院歯学研究科, 助教授 (50005039)
SUGAWARA Yumiko Hospital, Assistant, 病院・助手 (30235866)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2005: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | proteases / protease inhibitors / Immune regulation / protease-activated receptors / oral mucosa / saliva / oral mucosal diseases |
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| Research Abstract |
Research results of this project are as follows,
1. Trypsin-like protease produced by periodontopathic bacteria activated human gingival fibroblasts through protease activated receptor (PAR) 1 and PAR2, suggesting that this protease is critically involved in onset of periodontal disease.
2. Serum interleukin 18 (IL-18) levels and IL-18-dependent liver injury induced by LPS in Propionibacterium acnes-primed mice were significantly reduced by anti-Gr-1 injection (depletion of neutrophils). The same results were observed by co-administration of a serine protease inhibitor with LPS. A deficiency of PAR2 in mice significantly impaired IL-18 induction by treatment with P. acnes and LPS, and only slight pathological changes in hepatic tissues occurred in the PAR2^<-/-> mice treated with P. acnes and LPS. These results indicate that neutrophil recruitment and PAR2 activation by neutrophil serine proteases are critically involved in the induction of IL-18.
3. Lactoferrin (Lf) is an iron-binding an
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tibacterial protein, present in most exocrine secretions, such as saliva. In this study, we identified small Lf peptides in the saliva of chronic periodontitis patients and confirmed them to be fragments of intact Lf. Proteinase 3 (PR3) protein was detected in the saliva of periodontitis patients, and PR3 activity and levels of Lf fragments were correlation to the severity of clinical symptoms. Saliva Lf peptides showed no anti-bacterial activity against Escherichia coil; and had a reduced iron-chelating capacity. Saliva Lf peptides induce the production of pro-inflammatory cytokines in human oral epithelial cells. These results suggest that Lf in the parotid saliva of periodontitis patients was degraded into small peptides by the PR3-like activity with the capability to induce inflammatory mediators.
4. We identified soluble form of Toll-like receptor 2 (TLR2) in saliva. As TLR2 is an originally transmembrane receptor, it is suggested that some proteases are involved in the generation of soluble TLR2. We found that saliva modulated the TLR2-mediated immune responses in oral cavity Less
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