MECHANISMS OF INTERLEUKIN 11 IN GROWTH CONTROL

白介素 11 生长控制的机制

• 批准号: 2113039
• 负责人: Samuel Evans Adunyah
• 金额: $ 10.61万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2113039
• 关键词: autoradiography; biological signal transduction; calcium flux; calcium indicator; cell differentiation; cell growth regulation; cytokine; cytokine receptors; erythroleukemia; gene expression; genetic regulation; genetic transcription; hematopoietic growth factor; hematopoietic stem cells; immunofluorescence technique; myelogenous leukemia; neoplastic cell; oncogenes; posttranslational modifications; protein biosynthesis; protein kinase C; radiotracer; tissue /cell culture; western blottings

Interleukin-11 (IL-11) is a pleiotropic cytokine which has been shown to exhibit great clinical potential as a tool for the management and treatment of myelosuppressive syndrome caused by a great variety of conditions including cancer chemotherapy, physical and environmental factors. Although IL-11 has the potential to emerge as a clinical tool to treat bone marrow suppression, neutropenia and agranulocytosis associated radiation and chemotherapy, little is known about the mechanism by which it regulates hematopoietic progenitor cell growth and differentiation. The goal of this proposal is to understand how the binding of IL-11 to its receptor(s) leads to stimulation of expression of genes associated with erythroid and myeloid proliferation and differentiation. IL-11-R activation by IL-11 has been demonstrated to stimulate tyrosine phosphorylation of key signal transduction molecules and cause induction of expression of c-jun and c-fos mRNA. In addition, increases in levels of PK-C proteins occur in response to IL-11. These effects were associated with stimulation of leukemic cell growth by IL-11. In this proposal, we will (I) examine whether IL-11 regulates growth and differentiation of late erythroid and myeloid progenitor cells; (2) identify some of the key signal transduction molecules which mediate IL- 11 signaling to the nucleus and (3) determine whether IL-11 activates fos, jun and c-myc mRNA and protein synthesis. These studies will be conducted with cells grown in either conventional tissue culture incubators or NASA's ground-base bioreactors. The knowledge which will be obtained from this project will facilitate the clinic~1 evaluation of IL-11 for generation of normal functional tissues which can be utilized in the treatment of human diseases including cancer. The information can also be used to design drugs to block the neoplastic effects of IL-11.

白细胞介素 11 (IL-11) 是一种多效性细胞因子，已被证明可以 作为管理和治疗工具表现出巨大的临床潜力 治疗由多种原因引起的骨髓抑制综合征 条件包括癌症化疗、身体和环境 因素。尽管 IL-11 有潜力成为临床工具 治疗骨髓抑制、中性粒细胞减少症和粒细胞缺乏症 相关的放疗和化疗，人们对此知之甚少 其调节造血祖细胞生长的机制 差异化。该提案的目标是了解如何 IL-11 与其受体的结合会刺激表达 与红细胞和骨髓细胞增殖相关的基因 差异化。 IL-11 激活 IL-11-R 已被证明可以刺激酪氨酸 关键信号转导分子的磷酸化并引起诱导 c-jun 和 c-fos mRNA 的表达。此外，水平的增加 PK-C 蛋白的发生是对 IL-11 的反应。这些影响是 与 IL-11 刺激白血病细胞生长有关。 在本提案中，我们将 (I) 检查 IL-11 是否调节生长和 晚期红系和骨髓祖细胞的分化； (2) 鉴定一些介导 IL-的关键信号转导分子 11 向细胞核发出信号并 (3) 确定 IL-11 是否激活 fos、jun 和 c-myc mRNA 和蛋白质合成。这些研究将 使用传统组织培养中生长的细胞进行 孵化器或美国宇航局的地面生物反应器。这些知识将 从该项目中获得的结果将有助于临床〜1评估 IL-11 用于生成可利用的正常功能组织 用于治疗包括癌症在内的人类疾病。该信息可以 也可用于设计药物来阻断 IL-11 的肿瘤效应。