Bacterial cell surface amphiphiles and periodontal diseases - Study on the role of CD14 molecule in periodontal tissues -

细菌细胞表面两亲物与牙周疾病-CD14分子在牙周组织中的作用研究-

基本信息

批准号：
10470378
负责人：
TAKADA Haruhiko
金额：
$ 8.19万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Bacterial cell surface amphiphiles exhibit various biological activities. Endotoxic lipopolysaccharides (LPS) distributed in the outer membrane of gram-negative bacteria and lipoteichoic acid (LTA) distributed in the cell surfaces of gram-positive bacteria are representative bioactive amphiphiles. Bacterial amphiphiles activate host cells such as macrophages through membrane CD14 (mCD14) expressed on cell surfaces. Last year, we demonstrated the presence of two types of human gingival fibroblasts that highly and lowly express mCD14, and the former cells produced interleukin-8 (IL-8) upon stimulation with LPS and lipid A from Enterobacteriaceae. This year, we found that 1. Bacillus subtilis LTA also activated human gingival fibroblasts via mCD14, whereas LTA from oral streptococci such as Streptococcus sanguis and Streptococcus mutans acted as an LPS-antagonist to inhibit IL-8-induction by LPS. 2. The LPS fraction from Prevotella intermedia, periodontal disease-associated bacteria, activated human dental pulp cells that lack mCD14, in a soluble CD14- and nuclear factor AP-1-dependent manner. 3. Furthermore, in collaboration with Prof. Shizuo Akira, Osaka University, we studied the relationship between amphiphiles and the Toll-like receptor (TLR) system, which was recently revealed to be associated with CD14 and is involved in LPS signaling. We revealed that LTA as well as LPS was recognized by TLR4 in contrast to previous reports. We also obtained evidence suggesting that a bioactive glycoprotein, PGP, prepared from P. intermedia, was recognized by TLR2.With the viewpoint that "bacterial products overstimulate the innate immune system, and result in tissue destruction," we would like to reveal how the CD14/TLR system recognizes and responds to microbes in periodontal tissues in relation to the pathogenesis of periodontal diseases.

细菌细胞表面两亲物表现出各种生物学活性。分布在革兰氏阴性细菌的外膜和lipoteichoic酸（LTA）中的内毒性脂多糖（LPS）分布在革兰氏阳性细菌的细胞表面中是代表性的生物活性植物。细菌两亲物通过在细胞表面表达的膜CD14（MCD14）激活宿主细胞，例如巨噬细胞。去年，我们证明了两种类型的人牙龈成纤维细胞，它们高度低，低表达MCD14，而前一个细胞在用肠杆菌科刺激和脂质A刺激后产生了白介素-8（IL-8）。今年，我们发现1。枯草芽孢杆菌LTA还通过MCD14激活了人牙龈成纤维细胞，而口服链球菌的LTA（例如链球菌链球菌和链球菌突变体）充当LPS抗抗酸菌，以抑制IL-8-8诱导IL-8-诱导LPS。 2。以可溶性CD14和核因子AP-1依赖性方式，与Prevotella Intermedia（牙周疾病相关细菌）的LPS分数激活了缺乏MCD14的人类牙髓细胞。 3.此外，与大阪大学的Shizuo Akira教授合作，我们研究了两亲物与Toll-like受体（TLR）系统之间的关系，最近揭示的是与CD14有关，并参与LPS信号。我们透露，与以前的报告相比，TLR4认可了LTA和LPS。我们还获得了证据，表明由P. Intermedia制备的生物活性糖蛋白PGP得到了TLR的认可。与“细菌产物过度刺激了先天性免疫系统”并导致组织破坏的观点，我们希望如何揭示CD14/TLR系统识别和响应对微生物中的cd14/tlr系统的响应，以相关的是段落中的段落中的含量为中期的段落。