CDNA OF JANUSINE--A NOVEL IMMUNOMODULATORY MONOKINE

描述(摘自申请者摘要)：感染艾滋病毒的巨噬细胞 释放大量IL-1和一种新的7kd单核细胞因子 多效性：一方面抑制IL-1和IL-6诱导的 T淋巴细胞共生，另一方面刺激B细胞 有丝分裂。这种免疫调节单核因子被称为Janusine，因为 其看似相反的生物活性。据推测，贾努辛 在HIV感染和其他疾病的发病机制中发挥重要作用 免疫调节功能失调的状况。该计划的总体目标 研究的目的是克隆、表达和表征 贾努辛。在第一阶段，Janusine的全长cDNA克隆将 获得。利用mR-NA构建Lambda GT-11的cDNA文库 从脂多糖刺激的巨噬细胞或巨噬细胞系中 用中和免疫印迹阳性抗Janusine进行筛选 单抗。生物活性Janusine克隆将使用以下方法进行鉴定 Okayama-Berg载体在Cos-7细胞中的表达这个 将表达Janusine cdna并纯化蛋白以用于生物 学习。在第二阶段，Janusine的治疗潜力将是 已评估。Janusine的克隆可能为临床提供一种新的治疗方法 以不受控制的炎症为特征的疾病，如类风湿 关节炎。这种单核细胞因子的抑制剂可能有益于艾滋病或脓毒症 病人。

DESCRIPTION (Adapted from applicant's abstract):HIV infected macrophages release elevated quantities of IL1 and a novel 7kd monokine with pleiotropic activities: on the one hand it inhibits IL1 and IL6 induced T lymphocyte comitogenesis, on the other hand it stimulates B cell mitogenesis. this immunomodulatory monokine is called Janusine because of its seemingly opposite bioactivities. It is hypothesized that Janusine plays an important role in the pathogenesis of HIV infection and other conditions of dysfunctional immunoregulation. The overall goal of the research is to clone, express, and characterize the activities of Janusine. In Phase I, the full length cDNA clones of Janusine will obtained. cDNA libraries will be constructed in lambda gt 11 using mRNA from LPS stimulated hyamn macrophages or macrophage cell lines and screened using a neutralizing immunoblot positive anti-Janusine monoclonal antibody. Bioactive Janusine clones will be identified using expression in the Okayama-Berg vector transfected into Cos 7 cells. The Janusine cDNA will be expressed and protein purified for biological studies. In Phase II, the therapeutic potential of Janusine will be evaluated. The cloning of Janusine may provide a novel therapeutic for diseases characterized by uncontrolled inflammation such as rheumatoid arthritis. Inhibitors of this monokine may benefit AIDS or sepsis patients.