Examination of biological response to Porphyromonas gingivalis infection.

检查牙龈卟啉单胞菌感染的生物学反应。

基本信息

批准号：
16591859
负责人：
TSUKUBA Tomoko
金额：
$ 1.92万
依托单位：
KYUSHU 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

项目摘要

Porphyromonas gingivalis is the primary pathogenic agent of adult periodontitis and produces a unique class of virulence proteinases known as Arg-gingipains (Rgps) and Lys-gingipain (Kgp). We purified a 660-kDa cell-associated gingipain complex existing as a homodimer of two catalytically active monomers that comprises their catalytic and adhesin domains. Electron microscopy revealed that the complex was composed of a globular particle with 10-nm external diameter possessing one or two electron dense hole-like structures. Two-dimensional gel electrophoresis and immunoblot analyses revealed the complex includes lipopolysaccharide (LPS). The complex significantly degraded human type I collagen and elastin and strongly disrupted cell viability of human gingival fibroblasts and endotherial cells with higher efficiencies compared to the monomeric gingipains. The native complex little induced production of nitrogen dioxide (NO_2), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) b … More y macrophages, whereas the heat-denatured complex resulted in increased production of them. The results indicate the importance of the complex in evasion of host defense mechanisms as well as in host tissue breakdown. Many epidemiological studies suggest that periodontal infections are a risk factor for atherosclerosis. Repeated intravenous injection of wild-type P.gingivalis resulted in an increase in the area of atherosclerotic lesions as well as an increase in the serum concentration of low-density lipoprotein (LDL) cholesterol and a decrease in that of high-density lipoprotein (HDL) cholesterol in apolipoprotein (apo) E-knockout mice fed a high-fat diet. However, Rgp/Kgp-deficient P.gingivalis did not promoted the atherosclerotic lesions. The specific inhibitors against Rgp suppressed the promotion of atherosclerotic lesions induced by wild-type P.gingivalis. Proteolytic activity of Rgp thus appears to play a crucial role in the promotion of atherosclerosis by P.gingivalis infection. Less

牙龈卟啉单胞菌是成人牙周炎的主要致病剂，并产生一种独特的病毒蛋白酶，称为Arg-gyipains（RGPS）（RGP）和Lys-gyipain（KGP）。我们纯化了一个660 kDa细胞相关的牙龈复合物作为两个催化活性单体的同二聚体，该单体包括它们的催化和粘合剂结构域。电子显微镜表明，该复合物由具有10 nm外径的全局粒子组成，具有一个或两个电子密集的孔状结构。二维凝胶电泳和免疫印迹分析显示，该复合物包括脂多糖（LPS）。与单体gingipaiins相比，该复合物显着降解了人类I型胶原蛋白和弹性蛋白，并严重破坏人牙龈成纤维细胞和效率更高的效率的效率的细胞活力。天然复合物很少诱导的二氧化氮（NO_2），肿瘤坏死因子α（TNFα）和白介素6（IL-6）B…更多的y巨噬细胞，而热饱和复合物则导致其产生增加。结果表明，复合物在宿主防御机理以及宿主组织分解中的重要性。许多流行病学研究表明，牙周感染是动脉粥样硬化的危险因素。反复的静脉注射野生型杀伤症导致动脉粥样硬化病变区域的增加，以及低密度脂蛋白（LDL）胆固醇的血清浓度升高，而高密度脂蛋白（HDL）胆固醇（HDL）胆固醇的胆固醇（apolipopropopopoprotocopopopopopopopopopopopopotion-niet a Apo-Fat-Fat-Fat-Fat-Futotim-knk）的降低。然而，RGP/KGP缺陷型生殖器并未促进动脉粥样硬化病变。针对RGP的特异性抑制剂抑制了野生型生殖器诱导的动脉粥样硬化病变的促进。因此，RGP的蛋白水解活性似乎在吉利亚斯感染促进动脉粥样硬化中起着至关重要的作用。较少的