INOS AND COX2 CEREBRAL BLOOD VESSELS

INOS 和 COX2 脑血管

• 批准号: 6112277
• 负责人: Frank M Faraci
• 金额: $ 17.15万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112277
• 关键词: Adenoviridae; blood brain barrier; blood vessels; cell transformation; gene expression; genetic regulation; genetically modified animals; interleukin 10; laboratory mouse; nitric oxide synthase; prostaglandin endoperoxide synthase; transfection; transfection /expression vector; vascular endothelium; vascular resistance

Endothelial and neuronal isoforms of nitric oxide synthase (NOS) appear to play a major role in regulation of cerebral circulation. The overall objectives of this project is to examine the influence of inducible NOS II and inducible cyclooxygenase (COX-2) on cerebral blood vessels. Both NOS II and COX-2 may be expressed in blood vessels in response to proinflammatory stimuli and under some pathophysiologi-cal conditions. The investigators propose to examine the influence of NOS II and COX-2 on vascular tone and permeability of the blood-brain barrier, and to examine mechanisms which regulate expression of these genes. To define the role of NOS iI in cerebral vessels, studies will now be performed using two state-of-the-art molecular approaches - NOS II knockoutmice and local overexpression using adenoviral- mediated gene transfer of NOS II. The functional importance of nuclear factor-Kappa Beta in mediating these responses will be examined. There may be interactions between the NOS and COX systems. Studies in NOS II knockout mice will allow examination of the functional importance of COX-2 in the presence and absence of NOS II. Interleukin-10 (IL-10) is an anti-inflammatory cytokine which protects against endotoxin shock. The role of IL- 10 in blood vessels is not known. Using IL-10 knockout mice, we plan to examine the hypothesis that interleukin 10 is a major endogenous regulator of expression of NOS II and COX-2 in cerebral vessels. Preliminary data support this hypothesis. Thus, state-of-the-art approaches will be used to study the role of NOS II, COX-2, and IL-10 in cerebral blood vessels. The studies should provide new insight into regulation of the cerebral circulation. Expression of these genes may be important in brain under several pathophysiological conditions including meningitis, ischemia, and in response to inflammatory stimuli.

内皮型和神经型一氧化氮合酶(NOS) 似乎在调节脑循环方面起着重要作用。 该项目的总体目标是检查其影响 诱导型一氧化氮合酶II和诱导型环氧合酶(COX-2)的表达 脑血管。NOS II和COX-2可能都是 在血管中表达对促炎刺激的反应 在某些病理生理条件下。调查人员 建议研究一氧化氮合酶II和环氧合酶-2对血管内皮细胞的影响 血管张力和血脑屏障的通透性，以及 研究调节这些基因表达的机制。 为了确定一氧化氮合酶II在脑血管中的作用，现在将有研究 使用两种最先进的分子方法- NOSII基因敲除小鼠和使用腺病毒局部过度表达- 介导的一氧化氮合酶基因转移II.一氧化氮合酶的功能重要性 核因子-Kappa-Beta在调节这些反应中将是 检查过了。一氧化氮合酶和环氧合酶之间可能存在相互作用 系统。对NOS II基因敲除小鼠的研究将允许检查 环氧合酶-2的功能重要性 没有一氧化氮合酶II.白介素10(IL-10)是一种抗炎物质 防止内毒素休克的细胞因子。白介素2的作用 10在血管中的作用尚不清楚。使用IL-10基因敲除小鼠，我们 计划检验白介素10是一种主要 一氧化氮合酶II和环氧合酶-2表达的内源性调节 脑血管。初步数据支持这一假设。因此， 将使用最先进的方法来研究一氧化氮合酶的作用 II、COX-2、IL-10在脑血管中的表达。这些研究 应该为大脑的调节提供新的见解 发行量。这些基因的表达在大脑中可能很重要。 在包括脑膜炎在内的几种病理生理条件下， 缺血，以及对炎症刺激的反应。