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具有多种生物活性。内毒素脂多糖（LPS）和脂磷壁酸（LTA）是两亲分子中具有代表性的生物活性物质，分别分布于革兰氏阴性菌的外膜和革兰氏阳性菌的细胞表面。细菌两亲物通过在细胞表面上表达的膜CD 14（mCD 14）激活宿主细胞如巨噬细胞。去年，我们证明了存在两种类型的人牙龈成纤维细胞，高表达和低表达mCD 14，前一种细胞产生白细胞介素-8（IL-8）刺激后，LPS和脂质A从肠杆菌科。今年，我们发现1。枯草芽孢杆菌LTA还通过mCD 14激活人牙龈成纤维细胞，而来自口腔链球菌如血链球菌和变形链球菌的LTA作为LPS拮抗剂抑制LPS诱导的IL-8。2.来自中间普氏菌（牙周病相关细菌）的LPS组分以可溶性CD 14和核因子AP-1依赖性方式激活缺乏mCD 14的人牙髓细胞。3.此外，我们与大坂大学的Shizuo Akira教授合作，研究了两亲物与Toll样受体（TLR）系统之间的关系，该系统最近被发现与CD 14相关，并参与LPS信号传导。我们发现，LTA以及LPS被TLR 4识别，与以前的报道相反。本研究从“细菌产物过度刺激先天免疫系统，导致组织破坏”的观点出发，探讨CD 14/TLR系统对牙周组织中微生物的识别和应答与牙周病发病机制的关系。

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.