MONOCYTE DERIVED LIPID MEDIATORS AND CYTOKINES

单核细胞衍生的脂质介质和细胞因子

• 批准号: 6473492
• 负责人: JESSICA D TEW
• 金额: $ 13.46万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6473492
• 关键词: Actinobacillus actinomycetemcomitans; adolescence (12-20); antibody formation; antibody specificity; bacterial cytopathogenic effect; bactericidal immunity; cell growth regulation; clinical research; cooperative study; cytokine; dendritic cells; disease /disorder onset; enzyme linked immunosorbent assay; family genetics; flow cytometry; gene environment interaction; gene expression; growth factor; human subject; immunoglobulin G; leukocyte activation /transformation; monocyte; neutralizing antibody; platelet activating factor; polymerase chain reaction; prostaglandin E; radioimmunoassay; statistics /biometry

Project 3: Monocyte derived lipid mediators and cytokines in regulating IgG2 production in early-onset periodontitis (EOP). Patients with EOP frequently have elevated levels of serum IgG2, and patients with high levels of IgG2 reactive with the EOP pathogen A. actinomycetemcomitans have less severe disease. The ability to produce elevated levels of IgG2 is reproducible in vitro using peripheral blood leukocytes (PBL). Further analysis supports the concept that high IgG2 responses in PBL from EOP patients are regulated by monocytes. Recent data indicates that soluble factors produced by monocytes have the IgG2 enhancing activity. These results prompt the hypothesis that the profile of monocyte-derived cytokines and/or lipid mediators from EOP patients are altered and that the adjusted levels of these soluble factors are responsible for increased production of serum IgG2 in EOP. These results prompt the hypothesis is that the profile of monocyte-derived cytokines and/or lipid mediators from EOP patients are altered and that the adjusted levels of these soluble factors are responsible for increased production of serum IgG2 in EOP. Preliminary data indicated that antibodies against the IL- 1beta, IL-6, IL-18 and IL-12 inhibit IgG2 production. Similarly, receptor inhibitors for platelet activating factor (PAF) or inhibitors of prostaglandin E2 (PGE2) synthesis dramatically reduced the production of IgG2. Furthermore, addition of PAF, of PG32 selectively increased IgG2 production in culture whereas addition of IL-1alpha inhibited IgG2 production. Interesting, recent data from our group indicates that genes involved in determining the type and among of IL-1 made appear to be associated with the risk of developing EOP. Moreover, we recently found a subpopulation of cells spontaneously emerging in 3 to 5 days cultures of monocytes from LIP with the morphological features of dendritic cells (DC) and DC promote IgG2 production. In short, the monocyte/macrophage/DC products: IL-1alpha, IL-1beta, IL-6, IL-12, PGE2, and PAF all appear to influence production of IgG2 and some appear to selectively regulate IgG2: We now propose to confirm and extend these results using both PWM and specific antigen to elicit IgG2 production in an effort to determine the factors involved in monocyte/macrophage DC-mediated regulation of IgG2 responses. A better understanding of IgG2 production in an effort to determine the factors involved in monocyte/macrophage/DC-mediated regulation of IgG2 responses. A better understanding of IgG2 responses may lead to better control of EOP and other diseases where IgG2 plays a critical role in host defense.

项目 3：单核细胞衍生的脂质介质和细胞因子在调节早发性牙周炎 (EOP) 中 IgG2 的产生。 EOP 患者的血清 IgG2 水平经常升高，而 IgG2 水平与 EOP 病原体伴放线菌反应性高的患者病情较轻。使用外周血白细胞 (PBL) 可在体外重现产生升高水平 IgG2 的能力。进一步的分析支持这样的观点：EOP 患者 PBL 中的高 IgG2 反应是由单核细胞调节的。最近的数据表明，单核细胞产生的可溶性因子具有 IgG2 增强活性。这些结果提出了这样的假设：EOP 患者的单核细胞来源的细胞因子和/或脂质介质的谱发生了改变，并且这些可溶性因子的调整水平是 EOP 中血清 IgG2 产生增加的原因。这些结果提示这样的假设：EOP 患者的单核细胞来源的细胞因子和/或脂质介质的谱发生了改变，并且这些可溶性因子的调整水平是 EOP 中血清 IgG2 产生增加的原因。初步数据表明，针对 IL-1β、IL-6、IL-18 和 IL-12 的抗体可抑制 IgG2 的产生。同样，血小板激活因子 (PAF) 受体抑制剂或前列腺素 E2 (PGE2) 合成抑制剂可显着减少 IgG2 的产生。此外，添加PAF、PG32选择性地增加培养物中的IgG2产生，而添加IL-1α抑制IgG2产生。有趣的是，我们小组的最新数据表明，参与确定 IL-1 类型和种类的基因似乎与发生 EOP 的风险相关。此外，我们最近发现在 LIP 的单核细胞培养物 3 至 5 天中自发出现的细胞亚群具有树突状细胞 (DC) 的形态特征，并且 DC 促进 IgG2 的产生。简而言之，单核细胞/巨噬细胞/DC 产物：IL-1α、IL-1β、IL-6、IL-12、PGE2 和 PAF 似乎都影响 IgG2 的产生，并且有些似乎选择性调节 IgG2：我们现在建议使用 PWM 和特异性抗原来确认并扩展这些结果，以引发 IgG2 的产生，以确定参与单核细胞/巨噬细胞 DC 介导的 IgG2 反应调节的因素。更好地了解 IgG2 的产生，以确定参与单核细胞/巨噬细胞/DC 介导的 IgG2 反应调节的因素。更好地了解 IgG2 反应可能有助于更好地控制 EOP 和 IgG2 在宿主防御中发挥关键作用的其他疾病。