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The mechanism of endotoxin-induced vascular endothelial injury

内毒素引起血管内皮损伤的机制

基本信息

批准号：
11670278
负责人：
YOKOCHI Takashi
金额：
$ 2.43万
依托单位：
Aichi Medical University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670278/
关键词：
endotoxin nitric oxide LPS vascular endothelial cell TNF interferon-gamma inducible type NO synthase END-D cell 血管内皮細胞 CD14 組織因子 TF HUVEC DIC

项目摘要

Effect of interferon-gamma(IFN-γ), tumor-necrosis factor-alpha(TNF-α)and lipopolysaccharide(LPS)on nitric oxide(NO)production in mouse vascular aortic endothelial cell line END-D was examined. LPS, TNF-α, and a lower concentration of IFN-γ inhibited NO production in END-D cells, while a higher concentration of IFN-γ definitely enhanced it. The NO production induced by a high concentration of IFN-γ was further augmented in combination with LPS or TNF-α. In the sequential incubation of LPS and IFN-γ, the enhancement of NO production required the prior treatment with IFN-γ. Stimulation of END-D cells with a high concentration of IFN-γ led to the expression of inducible type NO synthase(iNOS). The augmentation of NO production by IFN-γ alone or in combination with LPS or TNF-α was completely blocked by several inhibitors of iNOS.It was strongly suggested that a higher concentration of IFN-γ itself enhanced NO production in END-D cells through the expression of iNOS.LPS and TNF-α exclusively modulated the activity of iNOS which expression was once tiggered by IFN-γ. On the other hand, a lower concentration of IFN-γ.LPS and TNF-α reduced NO production through down-regulating constitutive type NOS.It was suggested that proinflammatory cytokines may be involved in LPS-induced vascular endothelial injury via NO production.

研究了干扰素-γ (IFN-γ)、肿瘤坏死因子-α (TNF-α)和脂多糖（LPS）对小鼠血管主动脉内皮细胞系END-D一氧化氮（NO）生成的影响。LPS、TNF-α和较低浓度IFN-γ均抑制END-D细胞NO的产生，而较高浓度IFN-γ则明显促进其产生。高浓度IFN-γ诱导的NO生成在LPS或TNF-α联合作用下进一步增强。在LPS和IFN-γ的连续孵育中，NO生成的增强需要预先用IFN-γ处理。高浓度IFN-γ刺激END-D细胞导致诱导型NO合成酶（iNOS）的表达。IFN-γ单独或与LPS或TNF-α联合增加NO的产生被几种iNOS抑制剂完全阻断。结果表明，较高浓度的IFN-γ本身通过iNOS的表达增强了END-D细胞中NO的产生。LPS和TNF-α单独调节曾被IFN-γ触发的iNOS活性。另一方面，较低浓度的IFN-γ。LPS和TNF-α通过下调一氧化氮的组成型来减少一氧化氮的产生，提示促炎因子可能通过一氧化氮的产生参与了LPS诱导的血管内皮损伤。