Shapira L, Frolov I, Halabi A, Ben-Nathan D
Department of Periodontology, Hebrew University-Hasassah School of Dental Medicine, Jerusalem, Israel.
J Periodontol. 2000 Mar;71(3):476-81. doi: 10.1902/jop.2000.71.3.476.
Epidemiological studies have suggested that stress can alter the onset and progression of periodontal disease. However, the mechanisms involved are not clear. The present study was designed to examine whether the functional response of mouse macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS) is affected by experimental stress, and to investigate the role of corticosterone (CS) in the stress-related effects.
Two models of stress were used: emotional (isolation) and physical (cold). We measured thioglycollate-induced macrophage recruitment in vivo, and LPS-induced nitric oxide (NO) secretion by the macrophages in vitro. Two groups of mice were exposed to the stress conditions: isolation or cold. A third group was injected daily with CS, and a fourth group was used as a control (no stress). After 3 days of stress conditions, thioglycollate was injected into the peritoneal cavity. Four days later, peritoneal macrophages were isolated, counted, and cultured. The secretion of NO by the cultured cells was evaluated with and without P. gingivalis LPS stimulation.
The number of cells in the peritoneal lavage of stressed mice was significantly reduced in comparison to macrophages isolated from non-stressed animals. The number of macrophages from CS-treated mice did not differ from controls. NO secretion from unstimulated macrophages did not differ between the stressed and control groups. Stimulation of the macrophages with P. gingivalis LPS significantly enhanced NO secretion by macrophages from the control and stressed animals, but not by the CS-treated group. NO levels secreted by P. gingivalis-stimulated cells from the two stressed groups were significantly higher than the levels secreted by controls, and the isolation group released significantly higher levels than the cold group. Stimulation of the macrophages with P. gingivalis LPS and interferon (IFN)-gamma resulted in enhanced NO secretion in the 4 groups compared to LPS alone, with no significant differences between the groups.
The results suggest that experimental stress modulates the response of macrophages to inflammatory stimulants, and that CS is not the sole mediator involved. The presence of IFN-gamma in the culture may mask the functional differences induced by stress. The stress-induced upregulation of NO secretion might be involved in the accelerated periodontal destruction in stressed subjects.
流行病学研究表明，压力可改变牙周疾病的发生和发展。然而，其中涉及的机制尚不清楚。本研究旨在探讨牙龈卟啉单胞菌脂多糖（LPS）刺激的小鼠巨噬细胞的功能反应是否受实验性压力影响，并研究皮质酮（CS）在压力相关效应中的作用。
使用两种压力模型：情绪性（隔离）和生理性（寒冷）。我们在体内测量了巯基乙酸盐诱导的巨噬细胞募集，并在体外测量了LPS诱导的巨噬细胞一氧化氮（NO）分泌。两组小鼠暴露于压力条件下：隔离或寒冷。第三组每天注射CS，第四组用作对照（无压力）。在压力条件持续3天后，将巯基乙酸盐注入腹腔。四天后，分离、计数并培养腹腔巨噬细胞。在有和没有牙龈卟啉单胞菌LPS刺激的情况下，评估培养细胞的NO分泌。
与从非应激动物分离的巨噬细胞相比，应激小鼠腹腔灌洗中的细胞数量显著减少。CS处理小鼠的巨噬细胞数量与对照组无差异。未刺激的巨噬细胞的NO分泌在应激组和对照组之间没有差异。牙龈卟啉单胞菌LPS刺激巨噬细胞显著增强了对照组和应激组动物巨噬细胞的NO分泌，但CS处理组未增强。两个应激组中牙龈卟啉单胞菌刺激细胞分泌的NO水平显著高于对照组，且隔离组释放的水平显著高于寒冷组。与单独使用LPS相比，牙龈卟啉单胞菌LPS和干扰素（IFN）-γ刺激巨噬细胞导致4组的NO分泌增强，各组之间无显著差异。
结果表明，实验性压力调节巨噬细胞对炎症刺激物的反应，且CS不是唯一涉及的介质。培养中IFN-γ的存在可能掩盖了压力诱导的功能差异。压力诱导的NO分泌上调可能与应激受试者牙周破坏加速有关。
