LPS-MONOCYTE INTERACTIONS IN PERIODONTAL DISEASE

牙周疾病中 LPS-单核细胞的相互作用

• 批准号: 3220771
• 负责人: FRANK C NICHOLS
• 金额: $ 18.01万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-06-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3220771
• 关键词: Actinobacillus; Bacteroides; Salmonella typhimurium; human subject; interferons; interleukin 1; lipopolysaccharides; lymphocyte; monocyte; periodontitis; physical chemical interaction; prostaglandin E; secretion

Human monocytes release elevated levels of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). These soluble mediators possess certain proinflammatory, immunosuppressive and bone resorbing characteristics and may be important in the pathogenesis of periodontitis. Recently, we have examined the capacity of human monocytes to release these products following treatment with several LPS preparations isolated from suspected periodontal pathogens. LPS preparations promoted PGE2 and IL-1 release with the following relative potencies: Wolinella recta greater than or equal to Salmonella typhimurium greater than Actinobacillus actinomycetemcomintans greater than Bacteroides intermedius greater than B. gingivalis. In a preliminary clinical study, monocytes were isolated from dental patients with generalized severe adult periodontitis or age matched patients with little or no attachment loss. Patients with severe periodontitis released 2-3 fold more PGE2 than control patients when cells were treated with LPS preparations isolated from Salmonella typhimurium, Bacteroides intermedius, B. gingivalis and Actinobacillus actinomycetemcomintans. Surprisingly, IL-1 release was similar for severe periodontitis patients and controls. These findings suggest that LPS-mediated secretion of PGE2 from monocytes may be related to the susceptibility of an individual to periodontitis. Recently, we have determined that gamma interferon, a product of activated T lymphocytes, can specifically potentiate PGE2 and IL-1 release from monocytes treated with Bacteroides LPS but not Salmonella. We propose to examine monocyte secretory response to highly defined preparations of LPS, with or without gamma interferon, in patients with either severe periodontitis or no significant attachment loss. Secretion of PGE2 and IL-1 will be determined prior to the initiation of periodontal therapy, after initial therapy, immediately following surgical therapy and 4 months after the completion of all therapy. PGE2 will be quantitated by GC-MS and IL-1 will be quantitated by RIA. In addition, we will assess monocyte secretory responses for cells isolated from a limited number of patients with localized severe periodontitis. We hope to establish that LPS-mediated PGE2 release from monocytes is an inherent response which is not affected by periodontal therapy.

人单核细胞释放水平升高的白细胞介素 1 (IL-1) 和细菌刺激时的前列腺素 E2 (PGE2) 脂多糖（LPS）。 这些可溶性介体具有一定的 促炎、免疫抑制和骨吸收 特征并可能在发病机制中发挥重要作用 牙周炎。 最近，我们检查了人类的能力 单核细胞在治疗后释放这些产物 从疑似牙周组织中分离出几种 LPS 制剂 病原体。 LPS制剂促进PGE2和IL-1释放 具有以下相对效力： Wolinella 直肠更大 大于或等于鼠伤寒沙门氏菌大于 放线杆菌共生放线杆菌大于拟杆菌 intermedius 大于 B. gingivalis。 在初步临床 研究从牙科患者体内分离出单核细胞 全身性严重成人牙周炎或年龄匹配的患者 很少或没有依恋损失。 重症患者 牙周炎患者释放的 PGE2 比对照患者多 2-3 倍 当细胞用分离自的LPS制剂处理时 鼠伤寒沙门氏菌、中间拟杆菌、牙龈芽孢杆菌 和放线放线杆菌。 令人惊讶的是，IL-1 严重牙周炎患者和对照组的释放相似。 这些发现表明 LPS 介导的 PGE2 分泌 单核细胞可能与个体的易感性有关 牙周炎。 最近，我们确定伽玛 干扰素是活化T淋巴细胞的产物，可以特异性地 增强经处理的单核细胞的 PGE2 和 IL-1 释放 拟杆菌 LPS 但不是沙门氏菌。 我们建议审查 单核细胞对高度明确的制剂的分泌反应 LPS，无论有或没有γ干扰素，对于患有以下任一疾病的患者 严重牙周炎或无明显附着丧失。 分泌 PGE2 和 IL-1 的含量将在开始之前确定 牙周治疗，初始治疗后，立即 手术治疗和所有治疗完成后4个月。 PGE2 将通过 GC-MS 进行定量，IL-1 将进行定量 由RIA。 此外，我们将评估单核细胞分泌反应 对于从有限数量的局部患有局部疾病的患者中分离出的细胞 严重的牙周炎。 我们希望建立 LPS 介导的 单核细胞释放 PGE2 是一种固有反应，并非如此 受牙周治疗的影响。