Periodontal destruction and innate immunity via toll-like receptors
| Project/Area Number |
16591827
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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 |
Morphological basic dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
MIYAUCHI Mutsumi Hiroshima University, Graduate school of Biosphere Science, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (50169265)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Ikuko Hiroshima University, Hospital, Associate Professor, 病院・講師 (70136092)
KUDO Yasusei Hiroshima University, Graduate school of Biosphere Science, Research Associate, 大学院医歯薬学総合研究科, 助手 (50314753)
KITAGAWA Masae Hiroshima University, Hospital, Research Associate, 大学院医歯薬学総合研究科, 助手 (10403627)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | TLR4 Knock out mouse / Toll-like receptor / innate immunity / animal model for periodontitis / TLRノックアウトマウス / TLR4ノックアウトマウス / TRL4 / 免疫組織化学 / 動物実験 |
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| Research Abstract |
1) Mouse cementoblast cell line (OCCM-30), bone marrow stromal cell line (ST2), primary calvarial osteoblast (OB) and macrophage cell line (RAW) constitutively expressed toll-like receptors.
2) Stimulation of TLR4 pathway caused upregulation of TNF-α, IL-6 and RANKL mRNA and downregulation of OPG. The second peak of RANKL mRNA-expression caused by PGE2 production via cyclooxygenase-2 induction. Cell responses to TLR5 pathway were similar to those of TLR4 pathway. It was reported that stimulation of TLR4 or TLR5 induced upregulation of inflammatory cytokines production such as TNF-α, IL-6 and IL-8 resulted from NF-κB activation via common signaling pathway.
3) TLR9 pathway induced upregulation of IFN mRNA in addition to TNF-α and RANKL mRNA. Mechanisms of osteoclastogenesis via TLR9 pathway may be different from TLR4 pathway.
4) At 24 hours after LPS stimulation, downregulation of TLR4 mRNA level in ST2 or OCCM-30 cells was observed. The finding is supporting a result that the immuno-expre
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ssion of TLR4 was reduced in vivo periodontal tissue after topical application of LPS. On the other hand, after TLR9 activation with CpG-ODN there was no obvious difference in each TLR mRNA expression level. These findings indicate that in periodontal tissue toll-like receptors may be related to induction of innate immunity and development of periodontal disease after challenge of periodontal pathogens in a complex manner.
5) Single application of LPS to rat gingival sulcus could not induce B cell lesion in periodontal tissue like human periodontitis. Therefore two times of intraperitoneal injection of killed bacteria (Actinobacillus Actinomycetemcomitans, Aa 10mg/l rat) were done with one week interval. At one week after last injection mixture solution of 50g/ml OMP-29 and 1mg/ml Aa-LPS was treated into gingival sulcus. Although increase of serum level of antibody to OMP-29 was detected, B cell lesion in periodontal tissue was not developed. We will continuously try to establish mouse periodontitis model. Less
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Report
(3 results)
Research Products
(4 results)
