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Regulatory mechanism of expression of ODF and OCIF genes in P.gingivalis LPS-induced bone resorption.

ODF和OCIF基因表达在牙龈卟啉单胞菌LPS诱导骨吸收中的调控机制。

基本信息

批准号：
11671810
负责人：
AMANO Shigeru
金额：
$ 2.5万
依托单位：
Meikai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671810/
关键词：
LPS IL-6 ODF OCIF CD14 TLR4 骨吸収 IL-1β TNFα ST-2 破骨細胞形成

项目摘要

Lipopolysaccharid (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions, and one of these roles is a powerful stimulator of bone resorption. We have shown that endogenous CD14 plays an important role in LPS-stimulated bone resorption that is mediatedby IL-1β and IL-6 induced by the toxin. However, the mechanism by which LPS stimulates bone resorption is not yet understood. In the present study, we show using ST-2 cells having a supporting ability of osteoclast formation that LPS-induced osteoclast differentiation factor (ODF) gene expression in ST-2 cells is mediated by endogenous IL-6 via CD14-TLR4. We observed that LPS obviously stimulated expression of ODF gene in ST-2 cells. The LPS-induced expression of ODF gene was markedly neutralized by anti-mouse IL-6 antibody treatment. In addition, IL-6 was able to induce expression of ODF gene in ST-2 cells. These observations suggest that LPS-induced expression of ODF gene in ST-2 cells was mediated by indirect action of endogenous IL-6. On the other hand, ST-2 cells exhibited constitutive expression of CD14 and Toll-like receptor 4. The LPS-induced expression of IL-6 gene was clearly inhibited by PI-PLC treatment which was an enzyme from B.cereus which specifically cleaves the GPI anchor of CD14. In addition, LPS induction of ODF and IL-6 gene expressions was clearly stimulated in the TLR4-overexpressed ST-2 cells. These results suggested the functional role of CD14 and TLR4 in LPS responsibility of ST-2 cells. The present study thus clearly demonstrates a functional role of endogenous IL-6 via CD14-TLR4 signaling in LPS-stimulated expression of ODF gene.In conclusion, our present study suggests that LPS induce expression of ODF/RANKL/TRANCE/OPGL gene in mouse stromal ST-2 cells via CD14-TLR4 dependent endogenous IL-6.

脂多糖（LPS）是一种细菌细胞成分，在炎症反应中发挥多功能作用，其中一个作用是骨吸收的强有力刺激剂。我们已经证明内源性CD 14在LPS刺激的骨吸收中起重要作用，该骨吸收由毒素诱导的IL-1β和IL-6介导。然而，LPS刺激骨吸收的机制尚不清楚。在本研究中，我们使用ST-2细胞具有破骨细胞形成的支持能力，LPS诱导的破骨细胞分化因子（ODF）基因表达在ST-2细胞中是由内源性IL-6通过CD 14-TLR 4介导的。我们观察到LPS明显刺激ST-2细胞ODF基因的表达。LPS诱导的ODF基因表达被抗小鼠IL-6抗体处理显著中和。IL-6可诱导ST-2细胞ODF基因表达。这些观察结果表明，LPS诱导的ST-2细胞ODF基因的表达是通过内源性IL-6的间接作用介导的。另一方面，ST-2细胞表现出CD 14和Toll样受体4的组成型表达。LPS诱导的IL-6基因的表达被PI-PLC处理明显抑制，PI-PLC处理是来自B.cereus的特异性切割CD 14的GPI锚的酶。此外，LPS诱导的ODF和IL-6基因表达明显刺激TLR 4过表达的ST-2细胞。这些结果表明，CD 14和TLR 4在ST-2细胞的LPS应答中起作用。因此，本研究表明内源性IL-6通过CD 14-TLR 4信号途径在LPS刺激的ODF基因表达中发挥作用，提示LPS通过CD 14-TLR 4依赖的内源性IL-6诱导小鼠ST-2细胞ODF/RANKL/TRANCE/OPGL基因表达。