PIVOTAL REGULATOR IN NEURO-IMMUNE INTERACTIONS

描述：(改编自《调查者摘要》) 神经内分泌和免疫系统是双向交流的。确实有 没有公认的标记物来衡量他们的相互作用或障碍。神经肽 荷尔蒙和细胞因子调节这两个系统的细胞，但人们对此知之甚少 与表面受体结合的细胞内步骤和细胞 当细胞因子和神经肽交叉系统时的反应。这样做的目的是 项目的目的是开始了解这些多个信号如何在 细胞内水平以及随后改变免疫和/或神经内分泌 细胞功能。初步数据表明，信号通路汇聚并 相互影响转录因子核因子-kappaB的活性。这个 该项目分为三个目的，以调查核因子-kappaB是否具有 在免疫和神经内分泌系统信号的整合中起着关键作用。1) 凝胶漂移研究将确定神经肽的范围和特异性 激素和细胞因子影响淋巴和神经内分泌细胞中的核因子-kappB。 2)荧光素酶顺式报告基因系统将被用来测量 单个和多个神经肽和细胞因子对核因子-kappaB活性的影响 信号分子。此外，核因子-kappaB途径的特定抑制剂将是 用来以定量的方式确定调节这一过程的效果 转录因子对体外抗体和细胞因子的产生有影响。3) 最后，使用核因子-kappaB1基因敲除小鼠模型的研究将用于 核因子-kappaB组分对神经肽相对重要性的研究 以及细胞因子对淋巴和垂体功能的影响。这些研究将 显示核因子-kappaB通路在介导选择性 神经肽和细胞因子对免疫和神经内分泌相互作用的调节。 核因子-kappaB的抑制剂正在开发中，主要用于抗炎 探员们。了解核因子-kappaB在神经内分泌免疫中的作用 相互作用可能会提出新的标记物和治疗靶点。反过来，这些 可能对治疗涉及神经和精神疾病的影响很大 免疫系统，如重症肌无力或多发性硬化症。

DESCRIPTION: (Adapted from the Investigator's Abstract) The neuroendocrine and immune systems communicate bi-directionally. There are no accepted markers to measure their interactions, or disorders. Neuropeptide hormones and cytokines regulate cells of both systems, but little is known of the intracellular steps between binding to the surface receptors and cellular responses when cytokines and neuropeptides cross systems. The goal of this project is to begin to understand how these multiple signals are integrated at the intracellular level and subsequently alter immune and/or neuroendocrine cell function. Preliminary data suggest that the signal pathways converge and mutually affect the activity of the transcription factor, Nf-kappaB. The project is divided into three aims to investigate whether Nf-kappaB has a pivotal role in the integration of immune and neuroendocrine system signals. 1) Gel shift studies will determine the extent and specificity of neuropeptide hormones and cytokines to affect Nf-kappB in lymphoid and neuroendocrine cells. 2) A luciferase cis-reporter gene system will be used to measure changes in Nf-kappaB activity due to individual and multiple neuropeptide and cytokine signal molecules. Also, specific inhibitors of the Nf-kappaB pathway will be used to determine in a quantitative manner the effect modulating this transcription factor has on in vitro antibody and cytokine production. 3) Finally, studies using a Nf-kappaB1 gene knockout mouse model will be used for studies of the relative importance of this Nf-kappaB component for neuropeptide and cytokine effects on lymphoid and pituitary functioning. These studies will show the impact and specificity of the Nf-kappaB pathway in mediating selected neuropeptide and cytokine regulation of immune and neuroendocrine interactions. Inhibitors of Nf-kappaB are being developed, primarily as anti-inflammatory agents. Understanding the role of Nf-kappaB in neuroendocrine-immune interactions may suggest novel markers and therapeutic targets. In turn, these might have great impact for treatment of diseases involving the nervous and immune systems, such as myasthenia gravis or multiple sclerosis.