Periodontal destruction and innate immunity via toll-like receptors

通过 Toll 样受体进行牙周破坏和先天免疫

• 批准号: 16591827
• 负责人: MIYAUCHI Mutsumi
• 金额: $ 2.3万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591827/
• 关键词: 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

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 … More 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

1)小鼠成牙骨质细胞（OCCM-30）、骨髓基质细胞（ST 2）、原代颅骨成骨细胞（OB）和巨噬细胞（RAW）组成性表达toll样受体。通过环氧合酶-2诱导产生PGE 2导致RANKL mRNA表达的第二个峰值。细胞对TLR 5通路的反应与TLR 4通路相似。研究表明，TLR 4和TLR 5通过共同的信号通路激活NF-κB，诱导TNF-α、IL-6和IL-8等炎性细胞因子的产生; 3）TLR 9通路除了诱导TNF-α和RANKL mRNA的表达外，还诱导IFN mRNA的表达。LPS刺激后24 h，ST 2和OCCM-30细胞中TLR 4 mRNA表达下调，但OCCM-30细胞中TLR 4 mRNA表达下调。这一发现支持了一个结果，即免疫表达 ...更多信息 局部应用LPS后，TLR 4在体内牙周组织中的表达减少。而CpG-ODN激活TLR 9后，各TLRmRNA表达水平无明显差异。提示牙周组织中Toll样受体可能以复杂的方式参与牙周致病菌攻击后天然免疫的诱导和牙周病的发生发展。5）单纯应用LPS于大鼠龈沟不能诱导牙周组织中B细胞发生类似人类牙周炎的病变。因此，每隔一周进行两次腹腔注射灭活细菌（伴放线放线杆菌，Aa 10 mg/l大鼠）。最后一次注射后1周，将50 g/ml OMP-29和1 mg/ml Aa-LPS混合液注入龈沟内。虽然检测到血清抗OMP-29抗体水平升高，但牙周组织中的B细胞病变未发展。我们将继续尝试建立小鼠牙周炎模型。少

项目成果

Effects of endogenous and exogenous prostaglandin E2 on the proliferation and differentiation of a mouse cementoblast …

内源性和外源性前列腺素E2对小鼠成牙骨质细胞增殖和分化的影响......

• 发表时间: 2006
• 期刊: Journal of Periodontology 77
• 作者: Okamoto;S.;Tamura;Y.;Terao;Y.;Hamada;S.;Kawabata,S.;Ken-ichi Tezuka;Mada Y.et al.
• 通讯作者: Mada Y.et al.

Immuno-localization of COX-1 and COX-2 in the rat molar periodontal tissue after topical application of lipopoly…

局部应用脂多聚后，大鼠磨牙牙周组织中 COX-1 和 COX-2 的免疫定位...

• 发表时间: 2004
• 期刊: Archives of Oral Biology 49
• 作者: Terao;Y.;Okamoto;S.;Kataoka;K.;Hamada;S.;Kawabata;S.;Miyauchi M et al.
• 通讯作者: Miyauchi M et al.

Immuno-localization of COX-1 and COX-2 in the rat molar periodontal tissue after topical application of lipopolysaccharide.

局部应用脂多糖后大鼠磨牙牙周组织中 COX-1 和 COX-2 的免疫定位。

• 发表时间: 2004
• 期刊: Arch Oral Biol 49
• 作者: M Miyauchi;M Hiraoka;H Oka;S Sato;Y Kudo;I Ogawa;K Noguchi I Ishikawa;T Takata.
• 通讯作者: T Takata.