FEASIBILITY STUDY--IDENTIFY AND CHARACTERIZE ENDOTHELIAL INFLAMMATION GENES

可行性研究——内皮炎症基因的识别和表征

• 批准号: 5206155
• 负责人: GEFFREY S KANSAS
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5206155
• 关键词: SDS polyacrylamide gel electrophoresis; antisense nucleic acid; arthritis; autoimmune disorder; enzyme linked immunosorbent assay; gene expression; hybridomas; immunogenetics; immunoprecipitation; inflammation; molecular cloning; monoclonal antibody; northern blottings; nucleic acid hybridization; nucleic acid sequence; phenotype; polymerase chain reaction; protein structure function; tissue /cell culture; tumor necrosis factor alpha; vascular endothelium; western blottings

A central role for the vascular endothelium in inflammation has been appreciated for some time. However, the specific genetic programs responsible for induction and maintenance of an inflammatory state are only beginning to be identified and analyzed. An essential component of this analysis is the identification of genes which are expressed in endothelium activated by inflammatory stimuli, and which contribute to the leukocyte recruitment, morphological and biochemical changes in endothelium, and tissue damage characteristic of inflammation. This proposal details a broad approach to identifying such genes, and to identifying their possible role in inflammation. We will utilize a differential hybridization approach to identify genes which are expressed in endothelium activated by TNF-alpha, a prototypical inducer of inflammatory changes in endothelium, but which are not expressed in resting endothelium, and conversely, to identify genes whose expression is lost as a result of TNF-alpha treatment. Analysis of the function of these genes will be guided by their pattern of expression and homology to known genes and gene families. In addition, we will generate monoclonal antibodies which define activation-associated differences on the endothelial cell surface. This knowledge should provide the foundation for chemotherapeutic intervention in a broad range of inflammatory and autoimmune conditions, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, and related disorders.

血管内皮在炎症中的核心作用是 欣赏了一段时间。 然而，特定的基因程序 负责诱导和维持炎症状态的是 才刚刚开始被识别和分析 的重要组成部分 这种分析是鉴定在细胞中表达的基因， 内皮细胞被炎症刺激激活， 白细胞募集、形态学和生化变化 内皮和炎症特征的组织损伤。 这 该提案详细介绍了一种广泛的方法来识别这些基因， 确定它们在炎症中的可能作用。 我们将利用 差异杂交法鉴定表达的基因 在由TNF-α激活的内皮细胞中， 内皮细胞中的炎症变化，但不表达于 静息内皮细胞，相反，以确定基因的表达， 由于TNF-α治疗而丧失。 的作用分析 这些基因将由它们的表达模式和同源性指导 与已知基因和基因家族的联系 此外，我们将生成 定义激活相关差异的单克隆抗体， 内皮细胞表面。 这些知识应该提供 为广泛的化疗干预奠定了基础， 炎症和自身免疫性疾病，包括类风湿性关节炎， 多发性硬化、动脉粥样硬化和相关疾病。