EXPRESSION OF LPS-INDUCIBLE CYTOKINES BY HUMAN MONOCYTES

人单核细胞表达 LPS 诱导细胞因子

• 批准号: 6547147
• 负责人: M P HAYES
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6547147
• 关键词: colony stimulating factor; gene induction /repression; human tissue; interferon alpha; interferon gamma; interleukin 1; interleukin 12; lipopolysaccharides; messenger RNA; molecular cloning; monocyte; nuclear factor kappa beta; nucleic acid sequence; tumor necrosis factor alpha

The use of cytokines as therapeutic agents is complicated by the fact that they do not act in isolation. The dissection of cytokine networks reveals that most cytokines are highly regulated in response to the levels of other cytokines. The current focus is on LPS-mediated responses of human monocytes and their modulation by stimuli that affect monocyte differentiation, particularly interferon-gamma and colony-stimulating factors. This work has revealed that the induction of critical bio-active cytokines from monocytes can be highly influenced by the presence of these exogenous cytokines. The dependence upon, and effects of, priming differ with each monokine examined. For example, IL-12 is induced only after IFN-gamma priming, while IFN-alpha is induced following priming with either IFN-gamma or GM-CSF. Current studies are designed to identify critical intracellular factors that nediate these effects. This should provide useful information for understanding how cytokines interact in vivo, which should help predict the outome of in vivo responses to exogenous cytokines. This research reveals critical information about the capacity of specific cytokines to regulate the expression of other cytokines and affect differentiation of monocytes. Many of these cytokines are under current review in the division. We cannot have enough information about how these cytokines work in isolated circumstances, which gives rise to predictions about how they may function in vivo. In addition, this work requires continuing knowledge of methods for assessing the presence and activity of a variety of cytokines. Cytokine levels in sepsis patients have become important in patient monitoring and possibly in predicting outcome. Recent work in our laboratory is addressing the expression of IL-12 in dendritic cells. Currently, CBER is receiving numerous INDs proposing the use of dendritic cells in a variety of vaccines. Studies of IL-12 expression in dendritic cells will provide an excellent marker for the function and activity of these cells in vaccine products.

使用细胞因子作为治疗剂是复杂的事实， 他们不是孤立行动的 细胞因子网络的剖析 揭示了大多数细胞因子是高度调节的反应， 其他细胞因子的水平。 目前的重点是脂多糖介导的 人单核细胞的反应及其对影响 单核细胞分化，特别是干扰素-γ和 集落刺激因子 这项工作表明， 来自单核细胞的关键生物活性细胞因子可受到 这些外源性细胞因子的存在。 依赖，以及 启动效应因所检测的每种单核因子而异。 比如说， IL-12仅在IFN-γ引发后被诱导，而IFN-α仅在IFN-γ引发后被诱导。 在用IFN-γ或GM-CSF引发后诱导。 电流 研究旨在确定关键的细胞内因子， 消除这些影响。 这将提供有用的信息， 了解细胞因子如何在体内相互作用，这将有助于预测 体内对外源性细胞因子反应的外体。 这项研究揭示了关于特定的能力的关键信息， 细胞因子来调节其他细胞因子的表达， 单核细胞的分化。 这些细胞因子中的许多在电流下 在司内复查。 我们无法获得足够的信息 这些细胞因子在孤立的环境中起作用， 预测它们在体内的功能。 此外，这项工作 需要不断了解评估存在的方法， 多种细胞因子的活性。 脓毒症患者的细胞因子水平 在病人监测和预测 结果。 我们实验室最近的工作是解决 树突状细胞中的IL-12。 目前，CBER正在接收许多IND 提出将树突状细胞用于多种疫苗。 研究 IL-12在树突状细胞中的表达将提供一个极好的标志物， 这些细胞在疫苗产品中的功能和活性。