Rosen G, Sela M N, Naor R, Halabi A, Barak V, Shapira L
Department of Oral Biology, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel.
Infect Immun. 1999 Mar;67(3):1180-6. doi: 10.1128/IAI.67.3.1180-1186.1999.
We have recently demonstrated that the periodontopathogenic oral spirochete Treponema denticola possesses membrane-associated lipoproteins in addition to lipooligosaccharide (LOS). The aim of the present study was to test the potential of these oral spirochetal components to induce the production of inflammatory mediators by human macrophages, which in turn may stimulate tissue breakdown as observed in periodontal diseases. An enriched lipoprotein fraction (dLPP) from T. denticola ATCC 35404 obtained upon extraction of the treponemes with Triton X-114 was found to stimulate the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 (IL-1) by mouse macrophages in a dose-dependent manner. Induction of NO by dLPP was at 25% of the levels obtained by Salmonella typhosa lipopolysaccharide (LPS) at similar concentrations, while IL-1 was produced at similar levels by both inducers. dLPP-mediated macrophage activation was unaffected by amounts of polymyxin B that neutralized the induction produced by S. typhosa LPS. dLPP also induced NO and TNF-alpha secretion from macrophages isolated from endotoxin-unresponsive C3H/HeJ mice to an extent similar to the stimulation produced in endotoxin-responsive mice. Purified T. denticola LOS also produced a concentration-dependent activation of NO and TNF-alpha in LPS-responsive and -nonresponsive mouse macrophages. However, macrophage activation by LOS was inhibited by polymyxin B. These results suggest that T. denticola lipoproteins and LOS may play a role in the inflammatory processes that characterize periodontal diseases.
我们最近证明，牙周致病口腔螺旋体齿垢密螺旋体除脂寡糖（LOS）外还拥有膜相关脂蛋白。本研究的目的是测试这些口腔螺旋体成分诱导人巨噬细胞产生炎症介质的潜力，而炎症介质反过来可能刺激牙周疾病中观察到的组织破坏。在用 Triton X - 114 提取密螺旋体后从齿垢密螺旋体 ATCC 35404 获得的富集脂蛋白组分（dLPP），被发现以剂量依赖方式刺激小鼠巨噬细胞产生一氧化氮（NO）、肿瘤坏死因子α（TNF-α）和白细胞介素-1（IL-1）。在相似浓度下，dLPP 诱导的 NO 水平为鼠伤寒沙门氏菌脂多糖（LPS）诱导水平的 25%，而两种诱导剂诱导产生的 IL-1 水平相似。dLPP 介导的巨噬细胞激活不受多粘菌素 B 量的影响，多粘菌素 B 可中和鼠伤寒沙门氏菌 LPS 产生的诱导作用。dLPP 还诱导内毒素无反应性 C3H/HeJ 小鼠分离的巨噬细胞分泌 NO 和 TNF-α，其程度与内毒素反应性小鼠产生的刺激相似。纯化的齿垢密螺旋体 LOS 也在 LPS 反应性和非反应性小鼠巨噬细胞中产生浓度依赖性的 NO 和 TNF-α激活。然而，LOS 对巨噬细胞的激活受到多粘菌素 B 的抑制。这些结果表明，齿垢密螺旋体脂蛋白和 LOS 可能在表征牙周疾病的炎症过程中起作用。
