CDNA OF JANUSINE--A NOVEL IMMUNOMODULATORY MONOKINE

描述（改编自申请人摘要）：HIV感染的巨噬细胞 释放升高量的IL 1和一种新的7 kd单核因子， 多效性活性：一方面，它抑制IL 1和IL 6诱导的 T淋巴细胞共生，另一方面它刺激B细胞 有丝分裂 这种免疫调节因子被称为Janusine， 其看似相反的生物活性。据推测，Janusine 在HIV感染和其他疾病的发病机制中起重要作用。 免疫调节功能障碍的情况。 的总体目标 研究是克隆，表达，并表征的活动， Janusine 在第一阶段，Janusine的全长cDNA克隆将 得到了 cDNA文库将使用mRNA在λ gt 11中构建， 来自LPS刺激的Hyamn巨噬细胞或巨噬细胞细胞系， 使用中和免疫印迹阳性抗Janusine筛选 单克隆抗体 生物活性Janusine克隆将使用 在转染到Cos 7细胞中的Okayama-Berg载体中表达。 的 将表达Janusine cDNA并纯化蛋白质用于生物学用途。 问题研究 在第二阶段，Janusine的治疗潜力将是 评估。 Janusine的克隆可能会为人类提供一种新的治疗药物。 以不受控制的炎症为特征的疾病， 关节炎 这种单核因子的抑制剂可能有益于艾滋病或败血症 患者

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.