INTERLEUKIN 1 SYNTHESIS AND SECRETION

大量研究结果表明，白介素1(IL) 1)，一种由刺激产生的低分子蛋白质 巨噬细胞，也许还有其他几种细胞类型，都能显著地 影响细胞的成熟、功能激活和增殖 广泛的细胞类型，它们共同参与了 免疫或炎症反应。鉴于拟议的角色 IL 1在免疫和炎症中的作用，重要的是 了解IL-1合成的途径(S)及其调控， 释放、胞外处理及其作用机制。 在分子水平上的作用。因此，这一行动的主要目标是 建议包括： 为了阐明两国之间发生的一系列事件 33,000分子量(M.W.)的合成IL-1前体在 刺激的人和小鼠单核/巨噬细胞和 出现低MW值。细胞外IL-1(17-19,000) 环境；确定IL-1的氨基酸序列(S) 靶向分泌该蛋白质的前体； 确定IL-1前体中的氨基酸序列 作为细胞外加工的主要场所；以及 阐明钙促进分泌的机制 IL-1及其细胞外处理的影响。 在本提案中概述的工作中，我们将依赖于 前体和低分子质量人的重组形式 和小鼠IL-1，高度特异的抗IL-1抗体和IL-1 CDNAs探针。

The results from numerous studies indicate that interleukin 1 (IL 1), a low molecular weight protein produced by stimulated macrophages and perhaps several other cell types, can markedly affect the maturation, functional activation, and proliferation of a broad range of cell types that share a common involvement in immune or inflammatory responses. In view of the proposed role of IL 1 in immunity and inflammation, it is important to understand the pathway(s) and regulation of IL 1 synthesis, release, and extracellular processing, as well as its mechanism of action at the molecular level. Thus the major goals of this proposal are: To elucidate the sequence of events that occur between the synthesis of the 33,000 molecular weight (m.w.) IL 1 precursor in stimulated human and murine monocytes/macrophages and the appearance of low m.w. IL 1 (17-19,000) in the extracellular environment; to define the amino acid sequence(s) in the IL 1 precursor that serves to target this protein for secretion; to determine the amino acid sequences in the IL 1 precursor that serve as primary sites for extracellular processing; and to elucidate the mechanism by which calcium enhances the secretion of IL 1 as well as its extracellular processing. In the work outlined in this proposal, we will depend on the use of recombinant forms of precursor and low molecular weight human and murine IL 1, highly specific anti-IL 1 antibodies, and IL 1 cDNA probes.