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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.

观察干扰素-γ、肿瘤坏死因子-α(α)和脂多糖对小鼠血管内皮细胞株End-D产生一氧化氮(NO)的影响。脂多糖、肿瘤坏死因子-α和较低浓度的干扰素-γ抑制End-D细胞中NO的产生，而较高浓度的干扰素-γ则明显促进其产生。内毒素和肿瘤坏死因子-γ联合应用可进一步增强高浓度干扰素-α诱导的NO生成。在脂多糖和干扰素-γ的序贯孵育中，促进NO的产生需要预先用干扰素-γ处理。高浓度干扰素-γ刺激End-D细胞后，可诱导诱导型一氧化氮合酶表达。干扰素-γ单独或与脂多糖或肿瘤坏死因子-α联合应用均可完全阻断诱导型一氧化氮合酶的作用。提示较高浓度的干扰素-γ本身通过诱导型一氧化氮合酶的表达促进了End-D细胞中一氧化氮的产生。脂多糖和肿瘤坏死因子-α可独占地调节诱导型一氧化氮合酶的活性，而诱导型一氧化氮合酶的表达曾被干扰素-γ激活。另一方面，较低浓度的干扰素-γ、内毒素和肿瘤坏死因子-α通过下调构成型NO而减少NO的产生，提示促炎细胞因子可能通过NO的产生参与内毒素诱导的血管内皮损伤。