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: 3159029
• 负责人: GEORGE J FRIOU
• 金额: $ 13.32万
• 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/3159029
• 关键词: 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.

该项目的目标是解开这个谜团 硬皮病以使更有效的治疗成为可能 和/或预防措施。 在之前的研究中我们有 描述了一种 6-9,000 分子量的 IL-1 抑制剂 (IL-1)，由培养的人外周血单核细胞产生， 它具有充当刺激器的有趣特性 成纤维细胞。 培养患者外周血单核细胞 硬皮病会产生更多的 IL-1 抑制剂/成纤维细胞刺激剂与那些相比 正常人。 我们的研究计划旨在调查 以确定该物质是否还有其他特性 这将其与涉及的致病机制联系起来 硬皮病。 研究将包括调查 单核细胞的激活与该抑制剂的产生有关， 以及产生增加的单核细胞的特征 IL-1抑制剂/激活剂的量。 各种物质 已知可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，并且 是否有证据表明这种物质与硬皮病有关。 更多的 与该物质可能发挥的作用相关的远端区域 硬皮病也将被探索。 IL-1的产生，以及 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。 我们还将检查这种 IL-1 抑制剂对 成纤维细胞的细节相当多，包括其对 成纤维细胞增殖和胶原蛋白分泌 糖胺聚糖。 我们还计划研究它对其他方面的影响 相关的 IL-1 活性，例如刺激胶原酶 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/或可能的产生 涉及硬皮病和其他相关病症的组织，使用 现在有特定的单克隆抗体或寡核苷酸探针 正在开发中。 与该抑制剂的可能同一性 硬皮病血清因子以前被描述为成纤维细胞 促细胞分裂剂也将被研究。 我们的长期目标是 开发早期诊断、更有效治疗的方法， 治疗或预防硬皮病。