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BCMA expression in rheumatoid arthritis fibroblast-like synovial cells

类风湿性关节炎成纤维细胞样滑膜细胞中BCMA的表达

基本信息

批准号：
21890242
负责人：
NAGATANI Katsuya
金额：
$ 0.83万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Research Activity Start-up
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2010
项目状态：
已结题

项目摘要

Fibroblast-like synoviocytes(FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis(RA). We recently reported the variety of stimulating effects of a proliferation-inducing ligand(APRIL), and its specific effect on the FLS in the affected RA synovium(RA-FLS). A significantly higher level of soluble APRIL was detected in RA serum than in normal serum. Among the three receptors of APRIL tested, RA-FLS expressed only B cell maturation antigen(BCMA), whereas the FLS in the affected osteoarthritis synovium(OA-FLS) expressed none of the receptors. APRIL stimulated RA-FLS but not OA-FLS to produce interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β and APRIL itself. APRIL also enhanced the receptor activator of nuclear factor kappaB ligand(RANKL) expression in RA-FLS.The regulatory mechanisms of BCMA expression have not been fully described. OBF. 1 is a transcriptional co-activator, and has been shown to regulate the expression of PU. 1.In this study, we demonstrated that RA-FLS expressed transcription factor PU. 1 and transcriptional co-activator OBF. 1, and the expression levels of PU. 1 and OBF-1 were correlated with those of BCMA in RA-FLS.These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA. Epigenetic regulation of BCMA transcription might contribute to the underlying mechanisms of this condition. Thus, both BCMA and APRIL could be considered as potential therapeutic targets in ameliorating damage to the affected joints of patients with RA.

成纤维细胞样滑膜细胞（FLS）是类风湿关节炎（RA）发病机制中的主要效应细胞。我们最近报道了增殖诱导配体（APRIL）的各种刺激作用，以及其对受影响的RA滑膜（RA-FLS）中FLS的特异性作用。RA患者血清中可溶性APRIL水平显著高于正常人血清。在检测的APRIL的三种受体中，RA-FLS仅表达B细胞成熟抗原（BCMA），而受影响的骨关节炎滑膜中的FLS（OA-FLS）不表达任何受体。APRIL刺激RA-FLS产生白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、IL-1β和APRIL本身，但不刺激OA-FLS。APRIL还能增强RA-FLS中核因子κ B受体激活因子配体（RANKL）的表达。OBF。1是一种转录共激活因子，并已被证明可调节PU的表达。1.本研究证实RA-FLS表达转录因子PU。1和转录辅激活因子OBF。1，以及PU. RA-FLS中APRIL 1、OBF-1与BCMA的表达相关，提示APRIL是RA发病的主要调节因子之一。BCMA转录的表观遗传调控可能有助于这种情况的潜在机制。因此，BCMA和APRIL都可以被认为是改善RA患者受累关节损伤的潜在治疗靶点。