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首页> 外文期刊>Rheumatology >The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: implications in rheumatoid arthritis.
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The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: implications in rheumatoid arthritis.

机译：可溶性末端补体复合物（SC5b-9）上调骨保护素的表达和内皮细胞的释放：类风湿关节炎的影响。

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OBJECTIVE: Complement activation products contribute to a large number of inflammatory diseases, including RA. We have investigated whether osteoprotegerin (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the inflammatory cascade characterizing RA. METHODS: Levels of SC5b-9 and OPG in the plasma and SF of patients with active RA were determined by ELISA. The presence of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry. Cultured endothelial cells were used for in vitro leucocyte/endothelial cell adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order to evaluate the effects on the production of OPG protein, as well as the activation of the OPG promoter. RESULTS: Patients affected by active RA are characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells of post-capillary venules of RA synovial lesions. Data on endothelial cell cultures showed that exposure to SC5b-9 induced the up-regulation of OPG expression/release, stimulating the transcriptional activity of the OPG promoter, and synergized with TNF-alpha in up-regulating OPG production. CONCLUSIONS: Our findings demonstrate that SC5b-9 induces OPG production by endothelial cells and we propose that the SC5b-9-mediated up-regulation of OPG may be an important mechanism whereby complement contributes in promoting and/or enhancing the inflammation in RA.
机译：目的：补体激活产物导致包括RA在内的多种炎症性疾病。我们研究了骨保护素（OPG）是否与可溶性RA的可溶性末端补体复合物（SC5b-9）一致。方法：采用ELISA法测定活动性RA患者血浆和SF中SC5b-9和OPG的水平。通过免疫组织化学分析了RA滑膜病变中SC5b-9和OPG的存在。培养的内皮细胞用于体外白细胞/内皮细胞粘附测定。另外，将内皮细胞暴露于SC5b-9，以评估其对OPG蛋白产生的影响以及OPG启动子的激活。结果：患有活动性RA的患者的特征是血浆和/或SF中SC5b-9和OPG水平升高。值得注意的是，我们已经观察到RA滑膜病变的毛细血管后小静脉的内皮细胞中SC5b-9和OPG的共定位。内皮细胞培养物中的数据表明，暴露于SC5b-9会诱导OPG表达/释放的上调，刺激OPG启动子的转录活性，并在上调OPG产生中与TNF-α协同作用。结论：我们的发现证明SC5b-9诱导内皮细胞产生OPG，并且我们提出SC5b-9介导的OPG上调可能是补体有助于促进和/或增强RA炎症的重要机制。

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