NITRIC OXIDE REGULATION OF ENDOTHELIAL IL-8 EXPRESSION

一氧化氮对内皮 IL-8 表达的调节

• 批准号: 6125968
• 负责人: ALPHA Alsbury FOWLER
• 金额: $ 19.71万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6125968
• 关键词: binding sites; cell cell interaction; free radical oxygen; gene expression; genetic promoter element; genetic regulation; interleukin 8; neutrophil; nitric oxide; nuclear factor kappa beta; nucleoproteins; oxyhemoglobin; site directed mutagenesis; superoxides; tissue /cell culture; transcription factor; vascular endothelium

DESCRIPTION (adapted from applicant's abstract): Interleukin-8 (IL-8) is a proinflammatory peptide secreted by activated endothelial cells. Vascular injury frequently results from excessive IL-8 secretion during spesis, trauma, or ischemia-reperfusion injury. Nitric oxide (NO), which has many important physiological roles, can serve an anti-inflammatory role under conditions of intense endothelial activation but may be proinflammatory under other conditions and promote IL-8 secretion. Research performed by the applicant suggests that NO may have different regulatory actions on IL-8 gene expression depending on the activation state of the endothelium. The aims of the proposal are (1) to characterize the role of NO in stimulus-specific regulation of IL-8 expression in activated in vitro endothelium; (2) to define promoter regions of the IL-8 gene necessary for IL-8 induction in resting endothelium; (3) to identify transcription factors involved in mediating NO's effects on endothelial IL-8 expression; and (4) to use site-directed mutagenesis to confirm identity and activity of transcription factors conferring NO-responsiveness in promoter constructs. A number of different molecular techniques will be used to accomplish these aims. There is still an incomplete understanding of NO's regulation of inflammation, yet human trials of NO therapy for inflammatory injury of the lung are under way. A great deal remains to be learned about NO's role in the inflammatory process.

描述（改编自申请人的摘要）： 白细胞介素 8 (IL-8) 是一种促炎肽，由激活的细胞分泌。 内皮细胞。血管损伤常常是由于过度 脓毒症、创伤或缺血再灌注损伤期间 IL-8 的分泌。 一氧化氮（NO）具有许多重要的生理作用， 在强烈的内皮细胞条件下发挥抗炎作用 激活，但在其他条件下可能会促炎并促进 IL-8 分泌。申请人进行的研究表明，NO 可能 对 IL-8 基因表达具有不同的调节作用，具体取决于 内皮细胞的激活状态。该提案的目的是 (1) 表征NO在刺激特异性调节中的作用 体外激活的内皮细胞中IL-8的表达； (2) 定义 IL-8 基因的启动子区域是 IL-8 诱导所必需的 静息内皮细胞； (3) 鉴定参与的转录因子 介导 NO 对内皮 IL-8 表达的影响； (4) 使用 定点突变以确认其身份和活性 赋予启动子NO反应性的转录因子 构造。许多不同的分子技术将被用于 实现这些目标。目前还存在不完全的理解 NO 对炎症的调节，以及 NO 治疗的人体试验 肺部的炎症损伤正在发生。还有很多工作要做 了解 NO 在炎症过程中的作用。