The terminal complement complex C5b‐9 stimulates interleukin‐6 production in human smooth‐muscle cells through activation of transcription factors NF‐κB and AP‐1
The terminal complement complex C5b‐9 stimulates interleukin‐6 production in human smooth‐muscle cells through activation of transcription factors NF‐κB and AP‐1
复制标题
末端补体复合物 C5b-9 通过激活转录因子 NF-κB 和 AP-1 刺激人平滑肌细胞中白介素-6 的产生
DOI：
--
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
J. Kreuzer
中科院分区：
文献类型：
--
作者：
C. Viedt;G. Hänsch;R. Brandes;Wolfgang Kübler;J. Kreuzer
补体系统的激活在动脉粥样硬化的发病机制中起重要作用。促炎细胞因子白细胞介素（IL）-6可能参与疾病的进展。因此，我们研究了末端补体复合物C5 b-9是否影响血管平滑肌细胞（VSMC）产生IL-6，并着手确定潜在的信号转导途径。用C5 b-9刺激人VSMC导致IL-6转录物和IL-6蛋白的产生增加。用百日咳毒素或吡咯烷二硫代氨基甲酸酯预处理抑制补体依赖性IL-6 mRNA表达和IL-6释放，表明Gi蛋白和核因子-κ B（NF-κB）参与。C5 b-9还诱导活性氧的形成，其沿着IL-6的释放，被抗氧化剂N-乙酰半胱氨酸抑制。C5 B-9激活氧化还原敏感性转录因子NF-κB和激活蛋白-1（AP-1），这两种因子均参与C5 B-9诱导IL-6，如顺式元件双链（诱饵）寡核苷酸（ODN）所示。结果表明，补体系统的激活通过Gi依赖性途径诱导人VSMC释放IL-6，该途径涉及氧化应激的产生和氧化还原敏感性转录因子NF-κB和AP-1的激活。我们的数据支持一个新的机制，为致动脉粥样硬化的作用的末端补体复合物。
Activation of the complement system plays an important role in the pathogenesis of atherosclerosis. The proinflammatory cytokine interleukin (IL)‐6 is potentially involved in the progression of the disease. We therefore investigated whether the terminal complement complex C5b‐9 affects IL‐6 production from vascular smooth‐muscle cells (VSMC) and set out to determine the underlying signal transduction pathway. Stimulation of human VSMC with C5b‐9 resulted in an increase of IL‐6 transcript and production of IL‐6 protein. Pretreatment with pertussis toxin or pyrrolidine dithiocarbamate inhibited complement‐dependent IL‐6 mRNA expression and IL‐6 release, suggesting the involvement of Gi‐proteins and nuclear factor‐κΒ (NF‐κB). C5b‐9 also induced formation of reactive oxygen species, which, along with IL‐6 release, was inhibited by the antioxidant N‐acetylcysteine. C5b‐9 activated the redox‐sensitive transcription factors NF‐κB and activator protein‐1 (AP‐1), which were both involved in the induction of IL‐6 by C5b‐9, as demonstrated by cis element double‐stranded (decoy) oligonucleotides (ODN). The results demonstrate that activation of the complement system induces IL‐6 release from human VSMC by a Gi‐dependent pathway involving the generation of oxidative stress and the activation of the redox sensitive transcription factors NF‐κB and AP‐1. Our data support a new mechanism for the proatherogenic effect of the terminal complement complex.
影响因子：
8.7
作者：
Kranzhöfer, R;Schmidt, J;Kübler, W
通讯作者：
Kübler, W
末端补体复合物对鸟嘌呤核苷酸结合调节蛋白的受体非依赖性激活。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Niculescu,F;Rus,H;Shin,ML
通讯作者：
Shin,ML
液相 C5 转化酶激活人补体成分 C5。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
DiScipio,RG;Smith,CA;Muller-Eberhard,HJ;Hugli,TE
通讯作者：
Hugli,TE