FEASIBILITY STUDY--IDENTIFY AND CHARACTERIZE ENDOTHELIAL INFLAMMATION GENES

血管内皮细胞在炎症中的核心作用是 感激了一段时间。然而，具体的遗传程序 负责诱导和维持炎症状态的是 只是刚刚开始被识别和分析。的一个重要组成部分 这一分析是对表达在 由炎症刺激激活的内皮细胞，并有助于 白血球募集、形态和生化变化 血管内皮细胞和组织损伤的炎症特征。这 该提案详细介绍了识别此类基因的广泛方法，并 确定它们在炎症中可能扮演的角色。我们将利用一个 差异杂交法鉴定表达基因 在由肿瘤坏死因子-α激活的内皮细胞中， 血管内皮细胞炎性改变，但不表达于 静息内皮细胞，反之，识别其表达的基因 是肿瘤坏死因子-α治疗的结果。试析电子政务的功能 这些基因将由它们的表达模式和同源性来指导 已知的基因和基因家族。此外，我们还将生成 定义激活相关差异的单抗 内皮细胞表面。这一知识应该为 为广泛的化疗干预奠定基础 炎症和自身免疫性疾病，包括类风湿性关节炎， 多发性硬化症、动脉粥样硬化和相关疾病。

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.