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：在调节早期牙周炎（EOP）中调节IgG2产生的单核细胞衍生的脂质介质和细胞因子。 EOP患者的血清IgG2水平升高，IgG2高水平的患者与EOP病原体A. A.静脉炎的患者患有疾病。使用外周血白细胞（PBL），可以在体外重现产生升高水平的IgG2水平的能力。进一步的分析支持这样一个概念，即来自EOP患者的PBL的高IgG2反应受单核细胞调节。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。这些结果促使假设是，来自EOP患者的单核细胞衍生细胞因子和/或脂质介质的特征发生了改变，并且这些可溶性因子的调整水平是EOP中血清IgG2产生的增加。这些结果促使假设是，来自EOP患者的单核细胞衍生的细胞因子和/或脂质介质的特征发生了改变，并且这些可溶性因子的调整水平是EOP中血清IgG2产生的增加。初步数据表明，针对IL-1BETA，IL-6，IL-18和IL-12的抗体抑制IgG2产生。同样，用于血小板激活因子（PAF）或前列腺素E2（PGE2）合成的受体抑制剂大大降低了IgG2的产生。此外，添加PG32的PG32在培养中有选择地增加了IgG2的产生，而IL-1Alpha的添加抑制了IgG2的产生。有趣的，来自我们小组的最新数据表明，确定类型和IL-1的基因似乎与发展EOP的风险有关。此外，我们最近发现，从唇部的单核细胞中自发出现细胞的亚群，具有树突状细胞（DC）和DC的形态特征（DC）和DC促进IgG2的产生。 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介导的IgG2响应调节。对IgG2产生的更好理解是为了确定单核细胞/巨噬细胞/DC介导的IgG2响应调节的因素。对IgG2反应的更好理解可能会更好地控制EOP和其他疾病，其中IgG2在宿主防御中起着至关重要的作用。