C51, IL-8 AND FMLP RECEPTOR EXPRESSION BY GLIAL CELLS

补体的来源，疾病病理学的主要贡献者 如多发性硬化症（MS）和实验性过敏性脑脊髓炎 (EAE)，尚不清楚。 尽管缺乏信息， 补体在脱髓鞘疾病中的作用已被广泛研究。 这些 研究表明1）补体的末端组分的存在 其形成溶解性膜攻击复合物，2）补体激活 髓鞘和髓鞘碱性蛋白和3）的破坏性影响， 补体激活特异性炎症、脱髓鞘和组织 杀伤性 我们的初步数据表明，星形胶质瘤和 原代大鼠星形胶质细胞合成补体的几种成分 系统和合成可以被细胞因子显著上调， 干扰素-γ（IFN-γ）。 补体合成的调节 IFN-γ是特别令人感兴趣的，因为已知的所有其他细胞类型， 合成的补体对这种细胞因子的作用不敏感。 我们 假设在星形胶质细胞中， 细胞因子如IFN-γ的作用参与了 神经自身免疫性疾病，如MS或EAE。 由于补体介导的组织破坏的可能性， 在神经自身免疫性疾病的炎症，我们觉得这是重要的， 充分了解星形胶质细胞产生和调节补体的作用。 我们将重点关注参与替代激活的组件 补体途径（C3，因子B和D），因为所有这些组分都是 由星形胶质细胞瘤细胞和大鼠原代星形胶质细胞合成， 补体系统中的调节分子， 因子 我们将描述这些的生物合成和功能 组成部分所产生的星形胶质细胞瘤细胞系D54-MG，我们有 被发现是合成的代表性细胞类型 补体 我们还将研究IFN-γ对补体基因的诱导作用。 通过分析转录速率，稳态mRNA水平， mRNA稳定性和蛋白质表达。 此外，我们将描绘 组织特异性顺式和反式作用转录控制结构 星形胶质细胞瘤及大鼠C3基因表达调控 初级星形胶质细胞 本申请中提出的研究将有助于理解 补体在中枢神经系统中的作用。 此外，本发明还提供了一种方法， 这些信息将构成比较生产和 这些细胞类型对其他补体的调节，以及特定的 神经疾病状态，如MS和EAE。

The source of complement, a major contributor to the pathology of diseases such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), is unclear. Despite this lack of information, the role of complement in demyelinating disease has been extensively studied. These studies have shown 1) the presence of the terminal components of complement which form the lytic membrane attack complex, 2) activation of complement by myelin and myelin basic protein and 3) the destructive effects of complement activation specifically inflammation, demyelination and tissue destruction. Our preliminary data demonstrate that astrogliomas and primary rat astrocytes synthesize several components of the complement system and that synthesis can be markedly upregulated by the cytokine, interferon-gamma (IFN-gamma). The regulation of complement synthesis by IFN-gamma is of particular interest as all other cell types known to synthesize complement are refractory to the effect of this cytokine. We hypothesize that local complement production, enhanced in astrocytes by the effects of cytokines such as IFN-gamma, participates in the pathogenesis of neural autoimmune diseases such as MS or EAE. Because of the potential for complement-mediated tissue destruction and inflammation in neural autoimmune diseases, we feel it is important to more fully understand the production and regulation of complement by astrocytes. We will focus on components involved in the activation of the alternative pathway of complement (C3, factors B and D) as all of these components are synthesized by astroglioma cells and rat primary astrocytes, and on one of the regulatory molecules in the complement system, decay accelerating factor. We will characterize the biosynthesis and functionality of these components as produced by the astroglioma cell line D54-MG, which we have found to be a representative cell type with respect to synthesis of complement. We will also examine the induction of complement genes by IFN- gamma by the analysis of transcription rates, steady-state mRNA levels, mRNA stability and protein expression. Further, we will delineate the tissue-specific cis and trans-acting transcriptional control structures involved in regulation of C3 gene expression in astrogliomas and rat primary astrocytes. The studies proposed in this application will contribute to understanding the role played by complement in the central nervous system. In addition, this information will form the basis for comparing the production and regulation of other complement by these cell types, as well as in specific neural disease states such as MS and EAE.