SIL-1RA AND ICIL-1RA PRODUCTION BY MONOCYTE DERIVED CELL

白介素1受体拮抗剂(IL-1ra)以两种形式存在，即 通过备用起始点和单个 吉恩。分泌型IL-1ra(sIL-1ra)具有前导序列，是分泌的，是 单核细胞的重要产物，可能作为一种 细胞外IL-1的拮抗剂。细胞内IL-1ra(icIL-1ra)缺乏 前导序列可能主要保持在细胞内，是一种 上皮细胞的重要产物，并可能作为一种 细胞内IL-1的拮抗剂。将在这些文件中检验的假设 研究表明，单核/巨噬细胞同时产生sIL-1ra和sIL-1ra ICIL-1ra。进一步假设这两种形式的IL-1ra的产生 由这些细胞单独调节。四个具体目标将是 追求：1)准确定量sIL-1ra和icIL-1ra mRNA 定量PCR技术，2)准确定量sIL-1ra和sIL-1ra ICIL-1ra蛋白浓度利用灵敏和特异的ELISA法， 3)检测sIL-1ra和icIL-1ra mRNA的差异调节 和不同细胞类型中的蛋白质生产，以及4)检查 IcIL-1ra的潜在生物学作用。这些研究的结果应该是 阐明sIL-1ra和icIL-1ra在体内可能的相关性 类风湿性关节炎和其他慢性炎症性疾病。

Interleukin-1 receptor antagonist (IL-1ra) exists in two forms which are produced through alternate start sites and internal splicing of a single gene. Secretory IL-1ra (sIL-1ra) has a leader sequence, is secreted, is a significant product of monocytes, and probably functions as an antagonist of extracellular IL-1. Intracellular IL-1ra (icIL-1ra) lacks a leader sequence, probably remains predominantly intracellular, is a significant product of epithelial cells, and may function as an antagonist of intracellular IL-1. The hypothesis to be examined in these studies is that monocyte/macrophage cells produce both sIL-1ra and icIL-1ra. It is further hypothesized production of both forms of IL-1ra by these cells is regulated separately. Four specific aims will be pursued: 1) to accurately quantitate sIL-1ra and icIL-1ra mRNA utilizing quantitative PCR techniques, 2)to accurately quantitate sIL-1ra and icIL-1ra protein concentrations utilizing a sensitive and specific ELISA, 3) to examine the differential regulation of sIL-1ra and icIL-1ra mRNA and protein production in different cell types, and 4) to examine the potential biologic role of icIL-1ra. The results of these studies should clarify the possible in vivo relevance of sIL-1ra and icIL-1ra in rheumatoid arthritis and in other chronic inflammatory diseases.