Suppression of cytokines and nitric oxide production, and protection against lethal endotoxemia and viral myocarditis by a new NF-κB inhibitor
Suppression of cytokines and nitric oxide production, and protection against lethal endotoxemia and viral myocarditis by a new NF-κB inhibitor
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DOI：
10.1016/j.ejheart.2003.10.007
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发表时间：
2004-03-01
影响因子：
18.2
通讯作者：
Ono, K
中科院分区：
文献类型：
--
作者：
Matsumori, A;Nunokawa, Y;Ono, K
背景：核因子-κ B（NF-κ B）被多种因子激活，这些因子增加炎症反应，并且这种激活。进而导致几种基因如细胞因子的表达，并可能在心血管疾病中发挥重要作用。目的：研究一种新合成的NF-κ B抑制剂SUN C8079的体内外作用。研究方法：我们检测了SUN C8079对NF-κ B转录反应的影响，在电泳迁移率变动分析中对NF-κ B活化的影响，以及对肿瘤坏死因子（TNF）-α和iNOS基因表达的影响。并观察了SUN C8079对小鼠致死性内毒素血症和病毒性心肌炎的影响。结果如下：SUN C8079在体外通过抑制NF-κ B的活化来抑制脂多糖（LPS）诱导的TNF-α和iNOS基因的表达。SUN C8079抑制TNF-α的全身释放，并改善LPS处理小鼠的死亡率。除了保护小鼠免受致命的内毒素血症。SUN C8079可预防由脑心肌炎病毒（EMCV）引起的心肌炎，并抑制心肌组织中促炎细胞因子和iNOS基因的表达。结论：这些发现表明，NF-κ B的激活在内毒素血症和病毒性心肌炎的发病机制中起着重要作用，并且NF-κ B抑制剂SUN C8079可能在这些疾病中具有治疗作用。(C)2003年欧洲心脏病学会出版，Elsevier B. V.保留所有权利。
Background: Nuclear factor kappa B (NF-kappaB) is activated by several factors, which increase the inflammatory response, and this activation. in turn, leads to the expression of several genes such as cytokines, and may play an important role in cardiovascular diseases. Aims: The aim of the study is to examine the effect of SUN C8079, a newly synthesized NF-kappaB inhibitor in vitro and in vivo. Methods: We examined the effects of SUN C8079 on the transcriptional responses of NF-kappaB, on activation of NF-kappaB in electrophoretic mobility shift assay, and on the gene expressions of tumor necrosis factor (TNF)-alpha and iNOS. We also studied effects of SUN C8079 on lethal endotoxemia and viral myocarditis in mice. Results: SUN C8079 inhibited the lipopolysaccharide (LPS)-induced expression of the genes of TNF-alpha and iNOS by inhibiting the activation of NF-kappaB in vitro. SUN C8079 inhibited the systemic release of TNF-alpha and improved mortality in LPS-treated mice. In addition to protecting mice against lethal endotoxemia. SUN C8079 prevented the development of myocarditis due to the encephalomyocarditis virus (EMCV), and inhibited the expressions of proinflammatory cytokines and the iNOS gene in cardiac tissues. Conclusion: These findings suggest that the activation of NF-kappaB plays an important role in the pathogenesis of endotoxemia and viral myocarditis, and that the NF-kappaB inhibitor, SUN C8079, may be therapeutic in these disorders. (C) 2003 European Society of Cardiology Published by Elsevier B.V. All rights reserved.