SCOR ON THE PATHOGENESIS OF RHEUMATOID ARTHRITIS

我们建议建立类风湿性关节炎的症状自评量表 深入探讨类风湿性关节炎的发病机制 重视胶原自身免疫与关节发病机制 破坏和修复。具体而言，我们将致力于 以下问题：a)胶原蛋白自身免疫的性质 对小鼠的关节炎和耐受性负责，b) 不同关节胶原自身免疫性程度的研究 类风湿关节炎，c)结构功能的深入研究 白介素Lα、β与肿瘤靶细胞的关系 类风湿关节，d)基质降解的作用 类风湿中的金属蛋白酶及其抑制物 关节炎，e)评估IL-1、金属蛋白酶的作用 金属蛋白酶及其抑制剂的体内实验研究 胶原蛋白诱导的关节炎，以及f)详细研究 胶原蛋白基因表达调控机制的研究 结缔组织成纤维细胞。支持这些项目的将是 三个核心设施(杂交瘤、蛋白质化学和 行政)，旨在提供必要的 样品，材料，最先进的仪器和 拥有最高水平的技术和专业知识 以最具成本效益的方式参与项目。因此， 将采取的方法将是临床和基础两方面的 将涵盖细胞学和体液学的学科 免疫学、生物化学、细胞生物学、形态学和 除了风湿学，还有分子生物学。 这项提案中描述的研究只有通过 跨学科和协同合作将 继续在这一SCOR的调查人员中发展 申请。物质资源和智力环境 来自田纳西大学孟菲斯分校的 以获得必要的临床、动物和 为顺利完成 SCOR项目。考虑到过去的大量记录 在许多参与调查人员的合作下，有 完全有理由预测一个非常成功的SCOR将进一步 把这个群体聚集在一起，创造一个有利的环境 在处理这些问题的研究方面取得快速进展 类风湿性关节炎的发病机制。

We propose to establish a SCOR on rheumatoid arthritis in order to investigate the pathogenesis of RA in depth with special emphasis on collagen autoimmunity and the mechanisms of joint destruction and repair. Specifically, efforts will be directed at the following issues: a) the nature of collagen autoimmunity responsible for inducing arthritis and tolerance in mice, b) the degree of autoimmunity to a variety of different joint collagens in rheumatoid arthritis, c) in depth studies of the structure function relationships of interleukin l alpha and beta to target cells in the rheumatoid joint, d) the role of matrix degrading metalloproteinases and metalloproteinase inhibitors in rheumatoid arthritis, e) an assessment of the role of IL-1, metalloproteinases and inhibitors of metalloproteinases in vivo in experimental collagen induced arthritic, and f) a detailed study of the mechanisms involved in regulation of collagen gene expression in connective tissue fibroblasts. Supporting these projects will be three core facilities (Hybridoma, Protein Chemistry and Administrative) which are designed to provide the necessary samples, materials, state-of-the-art instrumentation and technical and professional expertise of the highest caliber to the participating projects in a most cost-effective manner. Thus, the approach to be taken will be both clinical and fundamental and will encompass the disciplines of cellular and humoral immunology, biochemistry, cell biology, morphology and molecular biology in addition to rheumatology. The research described in this proposal is possible only through the interdisciplinary and synergistic cooperation that would continue to develop among the investigators in this SCOR application. The physical resources and intellectual environment of the University of Tennessee, Memphis, are uniquely favorable for optimal performance of the necessary clinical, animal and bench research necessary for the successful completion of the SCOR projects. Given the substantial past track record of collaboration by many of the participating investigators, there is every reason to predict a very successful SCOR that will further bring this group together to create a conducive environment in which to make rapid progress in research dealing with the pathogenesis of rheumatoid arthritis.