PSS--ROLE OF IL-1 INHIBITOR/FIBROBLAST STIMULATOR

PSS--IL-1 抑制剂/成纤维细胞刺激剂的作用

• 批准号: 3159028
• 负责人: GEORGE J FRIOU
• 金额: $ 12.59万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3159028
• 关键词: AIDS; collagen; collagenase; fibroblast growth factor; fibroblasts; fibrosis; gene expression; human tissue; inflammation; interleukin 1; laboratory mouse; mitogens; mucopolysaccharides; oligonucleotides; scleroderma; secretion; tissue /cell culture

The objectives of this project are to unravel the mystery of scleroderma in order to make possible more effective therapy and/or preventive measures. In previous studies we have described a 6-9,000 molecular weight inhibitor of interleukin-1 (IL-1), produced by human peripheral blood monocytes in culture, which has the interesting characteristic of acting as a stimulator of fibroblasts. Cultured peripheral blood monocytes from patients with scleroderma produce increased amounts of this IL-1 inhibitor/fibroblast stimulator in comparison with those from normal individuals. Our research plan is designed to investigate this substance to determine if there are other characteristics which link it to the pathogenic mechanisms involved in scleroderma. The studies will include the investigation of monocyte activation, in relation to production of this inhibitor, and the characteristics of monocytes which produce increased amounts of the IL-1 inhibitor/activator. Various substances known to activate monocytes, as well as virus infection of monocytes, will be examined to determine whether any may selectively cause monocytes to produce this inhibitor, and whether evidence relates such a substance to scleroderma. More distal areas relating to a possible role for this substance in scleroderma will also be explored. Production of IL-1, and the low m.w. IL-1 inhibitor/fibroblast stimulator will be examined in other inflammatory and fibrotic states to determine if the latter are associated with selective increases in inhibitor production. We will also examine the action of this IL-1 inhibitor on fibroblasts in considerably greater dtail, including its effect on fibroblast proliferation and secretion of collagen and glycosaminoglycans. We also plan to study its effects on other related IL-1 activities such as stimulation of collagenase production by fibroblasts. We will examine tissues to determine the presence and/or possible production of the inhibitor in involved tissues in scleroderma and other related conditions, using a specific monoclonal antibody, or oliogonuclecotide probes now being developed. Possible identity with this inhibitor with scleroderma serum factors previously described as fibroblast mitogens will also be investigated. Our long term objective is to develop methods for early diagnosis, more effective treatment, cure, or prevention of scleroderma.

这个项目的目标是揭开神秘的 硬皮病，以使可能更有效的治疗 和/或预防措施。 在以前的研究中， 描述了一种分子量为6- 9，000的白细胞介素-1抑制剂， （IL-1），由培养的人外周血单核细胞产生， 它有一个有趣的特性， 成纤维细胞。 培养的患者外周血单核细胞 硬皮病患者产生更多的IL-1 抑制剂/成纤维细胞刺激剂与来自 正常的个体。 我们的研究计划旨在调查 以确定是否有其他特征 将其与致病机制联系起来， 硬皮病 这些研究将包括调查 单核细胞活化，与这种抑制剂的产生有关， 以及单核细胞的特性， 量的IL-1抑制剂/激活剂。 各种物质 已知激活单核细胞，以及病毒感染 单核细胞，将被检查，以确定是否有任何可能 选择性地使单核细胞产生这种抑制剂， 是否有证据表明这种物质与硬皮病有关 更 与该物质在以下方面的可能作用有关的远端区域： 还将探索硬皮病。 IL-1的产生， 低分子量IL-1抑制剂/成纤维细胞刺激剂将在 其他炎症和纤维化状态，以确定后者是否 与抑制剂产生的选择性增加有关。 我们还将研究这种IL-1抑制剂对 尾部成纤维细胞明显更大，包括其对 成纤维细胞增殖和胶原蛋白分泌， 糖胺聚糖 我们还计划研究其对其他 相关的IL-1活性，如刺激胶原酶 由成纤维细胞产生。 我们将检查组织以确定 抑制剂的存在和/或可能产生， 涉及硬皮病和其他相关疾病的组织，使用 一种特异性的单克隆抗体，或者寡核苷酸探针， 正在开发中。 可能与该抑制剂相同， 先前描述为成纤维细胞的硬皮病血清因子 还将研究促分裂剂。 我们的长远目标是 发展早期诊断的方法，更有效的治疗， 治疗或预防硬皮病。