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（根据申请人的摘要改编）： 白介素8（IL-8）是一种被激活的促炎肽 内皮细胞。血管损伤经常导致过多 IL-8分泌在SPES，创伤或缺血 - 再灌注损伤中。 一氧化氮（NO）具有许多重要的生理作用，可以 在强烈的内皮条件下发挥抗炎作用 激活但在其他条件下可能是促炎的，并促进 IL-8分泌。申请人进行的研究表明，没有 根据IL-8基因表达具有不同的调节作用 内皮的激活状态。该提议的目的是 （1）表征NO在刺激特异性调节中的作用 IL-8在活化的体外内皮中的表达； （2）定义 IL-8基因的启动子区域IL-8诱导中所需的启动子区域 静止的内皮； （3）确定涉及的转录因子 介导NO对内皮IL-8表达的影响； （4）使用 定向诱变，以确认 转录因子赋予启动子无反应性 构造。许多不同的分子技术将用于 实现这些目标。仍然有不完整的理解 NO的炎症调节，但没有治疗的人类试验 肺部的炎症损伤正在进行中。还有很多 了解NO在炎症过程中的作用。