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

白细胞介素-1受体拮抗剂（IL-1 ra）以两种形式存在， 通过交替的起始位点和内部剪接的单个 基因 分泌型IL-1 ra（sIL-1 ra）具有前导序列，被分泌， 单核细胞的重要产物，可能作为 细胞外IL-1的拮抗剂。 细胞内IL-1 ra（icIL-1 ra）缺乏 前导序列，可能主要保持在细胞内，是 上皮细胞的重要产物，并可作为 细胞内IL-1的拮抗剂。 在这些研究中要检验的假设 研究表明，单核细胞/巨噬细胞既产生sIL-1 ra， icIL-1ra。 进一步假设两种形式的IL-1 ra的产生 由这些细胞分别调节。 四个具体目标将是 目的：1）利用免疫荧光法准确定量sIL-1 ra和icIL-1 ra mRNA， 定量PCR技术，2）准确定量sIL-1 ra， 利用灵敏和特异性ELISA测定icIL-1 ra蛋白浓度， 3)研究sIL-1 ra和icIL-1 ra mRNA的差异调节 和蛋白质生产在不同的细胞类型，和4）检查 icIL-1 ra的潜在生物学作用。 这些研究的结果应该 阐明sIL-1 ra和icIL-1 ra在 类风湿性关节炎和其它慢性炎性疾病。

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.