PAF ACETYL-HYDROLASE IN LOCALIZED JUVENILE PERIODONTITIS

PAF 乙酰水解酶在局限性青少年牙周炎中的应用

• 批准号: 6954493
• 负责人: SUZANNE E BARBOUR
• 金额: --
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954493
• 关键词: SDS polyacrylamide gel electrophoresis; adolescence (12-20); antibody formation; carboxylic ester hydrolases; clinical research; cooperative study; disease /disorder onset; enzyme activity; enzyme linked immunosorbent assay; family genetics; gender difference; gene expression; human subject; immunoglobulin G; macrophage; periodontitis; platelet activating factor; smoking; statistics /biometry; thin layer chromatography; tissue /cell culture; tobacco abuse; western blottings

Project 4: PAF acetyhydrolase in localized juvenile periodontitis. Localized Juvenile Periodontitis (LJP) has a circumpurbertal onset and is characterized by severe destruction of the periodontal tissues surrounding the first molars and incisors. Although LJP has some of the clinical characterization of other periodontal diseases, it is clearly unique in terms of its mechanisms of pathogenesis and inheritance patterns. Among the immunological anomalies associated with LJP are the elevated levels of IgG 2 that are commonly found in the sera of LJP patients. Recent experiments suggest that IgG2 production is regulated by macrophage- derived lipid cytokines. Platelet activating factor (PAF), in particular stimulates IgG2 production, but has minimal effects on other isotypes of IgG. Preliminary data suggest that mononuclear cells from LJP patients express lower levels of PAF acetylhydrolase (PAF-AH), the enzyme that catabolizes PAF, then cells from periodontally healthy subjects. The decrease in PAF-AH activity could increase the availability of PAF and thereby stimulate IgG2 production in LJP patients. Hence, the goal of this research effort is elucidate the role of PAF-AH in the regulation of IgG2 production in LJP patients. Hence, the goal of this research effort is elucidate the role of PAF-AH in the regulation of IgG2 production in LJP patients. Experiments will be performed to determine whether mononuclear cells from LJP patients secrete less PAF-AH than cells from periodontally health subjects and if this enzyme is a negative regulator of IgG2 production. As preliminary studies indicate that mononuclear cells from LJP patients are predisposed to differentiate into dendritic cells, experiments will be performed to determine if dendritic cells express less PAF-AH than macrophages. Several lines of evidence indicate that both LJP and PAF-AH levels are heritable. Therefore, PAF-AH levels will be measured in the sera of LJP probands and their family members to determine if PAF-AH correlates with the incidence of the disease. Some cigarette smokers exhibit lower levels of serum IgG2 than non-smokers. This effect varies with the race and periodontal health status of the subject. Preliminary experiments indicate that there are higher levels of PAF-AH in the plasma of smokers than in non-smokers. Therefore, experiments will be performed to determine if PAF-AH is related to the reduction in serum IgG2 that is observed in cigarette smokers. Together, these studies should elucidate the role of PAF-AH in the regulation of IgG2 production. In addition, these experiments may yield insights into the genetic mature of LJP.

项目 4：PAF 乙酰水解酶治疗局部青少年牙周炎。局限性幼年性牙周炎（LJP）在青春期周围发病，其特征是第一磨牙和门牙周围的牙周组织严重破坏。尽管LJP具有其他牙周病的一些临床特征，但其发病机制和遗传模式显然是独特的。与 LJP 相关的免疫异常包括 LJP 患者血清中常见的 IgG 2 水平升高。最近的实验表明 IgG2 的产生受到巨噬细胞衍生的脂质细胞因子的调节。血小板激活因子 (PAF) 尤其会刺激 IgG2 的产生，但对其他 IgG 同种型的影响很小。初步数据表明，LJP 患者的单核细胞表达的 PAF 乙酰水解酶 (PAF-AH)（分解代谢 PAF 的酶）水平低于牙周健康受试者的细胞。 PAF-AH 活性的降低可以增加 PAF 的可用性，从而刺激 LJP 患者产生 IgG2。因此，这项研究工作的目标是阐明 PAF-AH 在调节 LJP 患者 IgG2 产生中的作用。因此，这项研究工作的目标是阐明 PAF-AH 在调节 LJP 患者 IgG2 产生中的作用。将进行实验以确定 LJP 患者的单核细胞分泌的 PAF-AH 是否比牙周健康受试者的细胞少，以及该酶是否是 IgG2 产生的负调节因子。由于初步研究表明来自 LJP 患者的单核细胞易于分化为树突状细胞，因此将进行实验以确定树突状细胞是否表达比巨噬细胞更少的 PAF-AH。多项证据表明 LJP 和 PAF-AH 水平都是可遗传的。因此，将测量 LJP 先证者及其家庭成员的血清中的 PAF-AH 水平，以确定 PAF-AH 是否与疾病的发病率相关。一些吸烟者的血清 IgG2 水平低于不吸烟者。这种效果随受试者的种族和牙周健康状况而变化。初步实验表明，吸烟者血浆中PAF-AH的含量高于不吸烟者。因此，将进行实验以确定 PAF-AH 是否与吸烟者中观察到的血清 IgG2 减少有关。总之，这些研究应该阐明 PAF-AH 在调节 IgG2 产生中的作用。此外，这些实验可能有助于了解 LJP 的遗传成熟度。