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.

研究了研究小鼠血管主动脉内皮细胞系端D中一氧化氮（NO）产生的干扰性γ（IFN-γ），肿瘤 - 肿瘤因子-Alpha（TNF-α）和脂多糖（LPS）的影响。 LPS，TNF-α和IFN-γ浓度较低会抑制END-D细胞中的NO产生，而较高浓度的IFN-γ肯定会增强它。由高浓度的IFN-γ引起的NO产生与LPS或TNF-α联合进一步增强。在LPS和IFN-γ的顺序孵育中，NO生产的增强需要先前对IFN-γ进行治疗。具有高浓度IFN-γ的末端D细胞刺激导致诱导型NO合酶（INOS）的表达。单独或与LPS或TNF-α结合使用的NO生产的增加完全被INOS的抑制剂完全阻断。强烈建议，IFN-γ本身通过表达Inos.LPS和TNF-α的表达，可以使INOS.LPS和TNF-α独立地调节Inos的表达的活性来增强END-D细胞的NO生成。另一方面，较低的IFN-γ.lps和TNF-α通过下调的构成型NOS型降低了NO的生产。这建议促炎细胞因子可能通过NO生产参与LPS诱导的血管内皮损伤。