Establishment of new treatment in rheumatoid arthritis under controlling nuclear factor KB activation.

建立控制核因子KB激活的类风湿性关节炎新疗法。

基本信息

批准号：
17591544
负责人：
HIRANO Fuminori
金额：
$ 2.3万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591544/
关键词：
signal transduction immunology nucleic acids clinical research gene regulation

项目摘要

We have studied that effect of NF-κB regulation in rheumatoid arthritis synovitis under controlling IκBβ2 expression in order to diminish the inflammation of synovitis. NF-κB is a transcription factor and plays a pivotal role in regulating synovitis in rheumatoid arthritis. In unstimulated cells, NF-κB binds to inhibitory molecules IκBs and exists in cytoplasm. Especially, IκBβ2 has the strongest inhibitory effect against NF-κB activation in IκBs. However, little is known about IκBβ2 expression and regulation in synovial cells with rheumatoid arthritis. First, we showed that IκBβ2 expression was significantly decreased in rheumatoid arthritis synovial cells as compared with in normal or osteoarthritis synovial cells. Moreover, when IκBβ2 was strongly expressed in synovial cells using expression plasmids, NF-κB activation was clearly repressed. Next, we have examined the half-life of IκBβ2 using 3'-untranslated lesion of IκBβ2-fused luciferase-gene expression plasmid. IκBβ2 half-life was shortening in rheumatoid arthritis synovial cells as compared with in normal or osteoarthritis synovial cells. In addition, we presented that several RNA binding proteins bound to 3'-untranslated lesion of IκBβ2 and those proteins were decreased or deleted in rheumatoid arthritis synovial cells. Collecting those results, the synovitis in rheumatoid arthritis was more strongly inflamed due to the decrease of IκBβ2 expression. We now investigate to clone new RNA binding proteins and to exam the function of those proteins.

我们已经研究了在控制IκBβ2表达以减少滑膜炎感染的情况下，NF-κB调节在类风湿关节炎滑膜炎中的影响。 NF-κB是转录因子，在调节类风湿关节炎中的滑膜炎中起关键作用。在未刺激的细胞中，NF-κB与抑制性分子IκB结合并存在于细胞质中。特别是，IκBβ2对IκB的NF-κB激活具有很强的抑制作用。但是，对于类风湿关节炎的滑膜细胞中的IκBβ2表达和调节知之甚少。首先，我们表明与正常或骨关节炎滑膜细胞相比，类风湿关节炎滑膜细胞中IκBβ2的表达显着降低。此外，当使用表达质粒在滑膜细胞中强烈表达IκBβ2时，NF-κB激活明显抑制。接下来，我们使用IκBβ2融合的荧光素酶基因表达质粒的3'-非翻译病变检查了IκBβ2的半衰期。与正常或骨关节炎细胞相比，类风湿关节炎滑膜细胞中IκBβ2半衰期正在缩短。此外，我们提出了与IκBβ2的3'-非翻译病变结合的几种RNA结合蛋白，这些蛋白在类风湿关节炎滑膜细胞中得到了改善或缺失。收集这些结果后，由于IκBβ2表达的降低，类风湿关节炎的滑膜炎受到更大的影响。现在，我们研究克隆新的RNA结合蛋白并检查这些蛋白质的功能。