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Experimental pathological study on roles of chemokines in LPS-induced periodontal tissue destruction - Basic analysis on remedical effects of specific antibody against chemokine -

趋化因子在LPS致牙周组织破坏中作用的实验病理学研究-趋化因子特异性抗体治疗作用的基础分析-

基本信息

批准号：
12671773
负责人：
MIYAUCHI Mutsumi
金额：
$ 2.11万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671773/
关键词：
chemokine Lipopolysaccharide MIP-2 TNF-α MCP-1 periodontitis Rat 好中球歯周炎 LPS

项目摘要

1. Immunoexpression of macrophage inflammatory protein-2 (MIP-2) and macrophage chemoattractant protein-1 (MCP-l) in rat periodontal tissue after topical application of Lipopolysaccharide (LPS) : 1) Topically applied 5 mg/ml E. Coli LPS from rat gingival sulcus rapidly provoked inflammatory changes in junctional epithelium (JE) and sub-JE area. In addition, stimulation of osteoclastic bone resorption along the alveolar bone surface showing a biphasic response peaking at 3 hours and 3 days was observed. 2) A transient immuno-expression of MIP-2 in JE cells peaking at 1 day was observed. Corresponding to excessive MIP-2 expression, LPS application induced a significant increase in number of neutrophils in JE and sub-JE area. 3) At day 1 and 2 after LPS application, immunoexpression of MCP-1 in osteoblasts and osteocytes presented in alveolar crestal area was observed. The MCP-1 production from these cells may cause local recruitment of preosteoclasts and the following osteoclastic bone r … More esorption at day 3.2. Application of various concentrations of MIP-2 : Various concentrations of recombinant rat MIP-2 (0.05, 0.5, 5, 50 μg/ml) applied from gingival sulcus caused not only neutrophil recruitment into JE and sub-JE area but also osteoclasts amassment along the alveolar bone surface in a dose dependent manner3. Effects of previously intraperitoneal-injected anti-MIP-2 antibody on periodontal tissue destruction caused by LPS-application : Injection of the anti-MIP-2 antibody remarkably reduced the recruitment of neutrophils into JE and sub-JE area and significantly decreased the appearance of osteoclasts at 3 days after LPS application. On the other hand, the first increase of osteoclasts at 3 hours, which is seemed to be a direct effect of LPS, was not inhibited by the anti-MIP-2 antibody treatment. Theses findings indicated that MIP-2 may be one of powerful CXC-chemokines for neutrophil recruitment into the periodontal disease site and may play an important role in the initiation of inflammation. Moreover, the over secretion of CXC-chemokine in the periodontal disease site may induce production of various osteoclast stimulating factors resulting in the subsequent alveolar bone destruction. It is suggested a possibility of establishment new periodontal therapy targeting CXC-chemokine. Less

1.局部应用脂多糖（LPS）后大鼠牙周组织中巨噬细胞炎性蛋白-2（MIP-2）和巨噬细胞趋化蛋白-1（MCP-1）的免疫表达：1）局部应用5 mg/ml E.大鼠龈沟内的大肠杆菌脂多糖可迅速引起龈沟交界上皮（JE）及JE下区的炎症反应。此外，还观察到沿牙槽骨表面沿着骨吸收的骨细胞刺激，显示出在3小时和3天达到峰值的双相反应。2)MIP-2在JE细胞中的瞬时免疫表达在第1天达到峰值。与MIP-2过度表达相对应，LPS应用诱导了JE和JE亚区中性粒细胞数量的显著增加。3)LPS刺激后第1、2天，观察MCP-1在牙槽嵴区成骨细胞和骨细胞中的免疫表达。这些细胞产生的MCP-1可能引起破骨细胞前体的局部募集，并导致随后的骨形成。 ...更多信息在第3.2天吸附。不同浓度MIP-2的应用：从龈沟应用不同浓度的重组大鼠MIP-2（0.05、0.5、5、50 μg/ml）不仅导致中性粒细胞募集到JE和JE下区域，而且还导致破骨细胞以剂量依赖性方式沿着牙槽骨表面扩增3。预先腹腔注射抗MIP-2抗体对LPS应用引起的牙周组织破坏的影响：注射抗MIP-2抗体显著减少了中性粒细胞向JE和JE下区域的募集，并显著减少了LPS应用后3天破骨细胞的出现。另一方面，在3小时时破骨细胞的首次增加（这似乎是LPS的直接作用）不被抗MIP-2抗体处理抑制。这些结果表明，MIP-2可能是一个强大的CXC趋化因子的中性粒细胞募集到牙周病部位，并可能在炎症的启动中发挥重要作用。此外，牙周病部位CXC趋化因子的过度分泌可诱导各种破骨细胞刺激因子的产生，导致随后的牙槽骨破坏。提示以CXC趋化因子为靶点建立新的牙周治疗方法的可能性。少