Selective inhibition of inhibitory kappa B kinase‐β abrogates induction of nitric oxide synthase in lipopolysaccharide‐stimulated rat aortic smooth muscle cells
Selective inhibition of inhibitory kappa B kinase‐β abrogates induction of nitric oxide synthase in lipopolysaccharide‐stimulated rat aortic smooth muscle cells
复制标题
选择性抑制抑制性 kappa B 激酶-β 消除脂多糖刺激的大鼠主动脉平滑肌细胞中一氧化氮合酶的诱导
DOI:
10.1038/sj.bjp.0706308
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发表时间:
2005
影响因子:
7.3
通讯作者:
R. Plevin
中科院分区:
文献类型:
--
作者:
A. B. Gómez;C. MacKenzie;A. Paul;R. Plevin
In this study, we utilised a number of adenoviral constructs in order to examine the role of intermediates of the NF‐κB pathway in the regulation of inducible nitric oxide synthase (iNOS) induction in rat aortic smooth muscle cells (RASMCs). Lipopolysaccharide (LPS) stimulated a significant increase in iNOS induction and NF‐κB DNA binding. These parameters were substantially reduced by overexpression of a wild‐type Iκ‐Bα adenoviral construct (Ad.Iκ‐Bα), confirming a role for NF‐κB in iNOS induction. Infection with a dominant‐negative IKKα adenoviral construct (Ad.IKKα+/−) did not significantly affect iNOS induction, NF‐κB DNA binding or Iκ‐Bα loss. Infection of RASMCs with adenovirus encoding a dominant‐negative IKKβ (Ad.IKKβ+/−) essentially abolished iNOS induction and activation of the NF‐κB pathway. Pretreatment of RASMCs with a novel specific inhibitor of IKKβ, SC‐514, significantly reduced iNOS induction, NF‐κB DNA binding and I‐κBα loss in a concentration‐dependent manner. In both RASMCs and human umbilical vein endothelial cells (HUVECs), infection with Ad.IKKβ+/− also inhibited COX‐2 expression in response to LPS. However, Ad.IKKα+/− was again without effect. These data suggest that IKKβ plays a predominant, selective role in the regulation of NF‐κB‐dependent induction of iNOS in RASMCs.
影响因子:
4.4
作者:
E. Faure;L. Thomas;H. Xu;A. Medvedev;O. Equils;M. Arditi
通讯作者:
E. Faure;L. Thomas;H. Xu;A. Medvedev;O. Equils;M. Arditi
影响因子:
3.7
作者:
Wang, Yanxin;Lv, Yuqiang;Li, Zilong;Gao, Min;Yang, Xiaomeng;Li, Yue;Shi, Jianguo;Gao, Zaifen;Liu, Yi;Gai, Zhongtao
通讯作者:
Gai, Zhongtao
影响因子:
7.4
作者:
Rattan, R;Giri, S;Singh, I
通讯作者:
Singh, I