CONNECTIVE TISSUE ACTIVATION IN RHEUMATIC DISEASES

风湿性疾病中的结缔组织激活

• 批准号: 3154723
• 负责人: C WILLIAM CASTOR
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-02-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3154723
• 关键词: antirheumatic agents; chemical structure function; collagenase; colorimetry; cortisol; cyclic AMP; cycloheximide; fibroblasts; granuloma; human tissue; hyaluronate; inflammation; paper chromatography; peptides; proteoglycan; rheumatism; rheumatoid arthritis; synovial fluid; synovitis; tissue /cell culture

We propose to isolate selected Connective Tissue Activating Peptides (CTAPs), and to define their chemical characteristics at a molecular level. Immunologic methods will be used to identify, localize and quantitate relevant human CTAPs in biological samples. Knowledge of the mechanisms of action of this class of regulators of connective tissue metabolism will be extended by identifying factors controlling synthesis and release of CTAPs, by defining the events occurring at the time of mediator-cell interaction, and by elucidating early consequences of activation (altered transport) as well as late events (glycosaminoglycan and proteoglycan synthesis). Relevance to rheumatic disease in man will be defined by studies of distribution and concentration of CTAPs in normal individuals and rheumatic patients, as well as by testing the therepeutic potential of selected agonists. Further, the activated human cell culture system will continue to be used as a model to test agents with potential for interdicting the inflammatory process. Our long-term objective is to sufficiently understand the mechanisms regulating connective tissue metabolism in normal man, and in degenerative and inflammatory processes, so that intelligent definitive intervention may become possible in rheumatic diseases.

我们建议分离精选的结缔组织激活肽 (CTAP)，并在分子水平上定义它们的化学特性 水平。将使用免疫学方法来识别、定位和 对生物样品中相关的人类CTAP进行定量。了解以下内容 这类结缔组织调节剂的作用机制 新陈代谢将通过识别控制合成的因素来延长 和CTAP的发布，通过定义在以下时间发生的事件 介体-细胞相互作用，并通过阐明早期后果 激活(改变运输)以及晚期事件(糖胺多聚糖 和蛋白多糖合成)。与人类风湿病的相关性将是 通过对正常人群中CTAP分布和浓度的研究确定 个人和风湿病患者，以及通过测试这些指标 选定激动剂的潜力。此外，活化的人类细胞培养物 系统将继续用作测试具有潜力的代理的模型 用来阻断炎症过程。我们的长期目标是 充分了解结缔组织的调节机制 在正常人的代谢过程中，在退行性和炎症过程中， 从而使智能的决定性干预成为可能 风湿病。