Ota Fumie, Maeshima Akito, Yamashita Shin, Ikeuchi Hidekazu, Kaneko Yoriaki, Kuroiwa Takashi, Hiromura Keiju, Ueki Kazue, Kojima Itaru, Nojima Yoshihisa
Gunma University School of Medicine, Maebashi, Japan.
Arthritis Rheum. 2003 Sep;48(9):2442-9. doi: 10.1002/art.11249.
To investigate the expression of activin A and its receptors in rheumatoid arthritis (RA) synovial tissues, and to determine the effect of activin A on cultured fibroblast-like synoviocytes (FLS).
The localization of activin A and activin type II receptor (ARII) in synovial tissues of RA patients was analyzed by immunohistochemistry. The expression of activin A and activin receptors in human cultured FLS was examined by reverse transcriptase-polymerase chain reaction and Western blotting. Enzyme-linked immunosorbent assay was used to measure activin A in culture supernatants. The cell growth of FLS was determined by (3)H-thymidine incorporation and MTT assay.
Immunohistochemical analysis confirmed the up-regulation of activin A in rheumatoid synovium as compared with osteoarthritis or normal joint tissues. CD68+ macrophage-lineage cells and vimentin-positive FLS were identified as activin-producing cells in rheumatoid synovium. Both cell types also expressed ARII. The expression of activin A and ARII on cultured FLS was confirmed at the protein and messenger RNA levels. Interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, and transforming growth factor beta activated FLS to secrete activin A. Recombinant activin A accelerated the proliferation of FLS, while follistatin, an endogenous activin antagonist, partially inhibited FLS proliferation induced by IL-1 beta.
These results suggest that activin A acts as a growth factor of FLS in RA.
研究激活素A及其受体在类风湿关节炎（RA）滑膜组织中的表达，并确定激活素A对培养的成纤维样滑膜细胞（FLS）的作用。
采用免疫组织化学分析法检测RA患者滑膜组织中激活素A和激活素II型受体（ARII）的定位。通过逆转录聚合酶链反应和蛋白质印迹法检测人培养的FLS中激活素A和激活素受体的表达。采用酶联免疫吸附测定法测量培养上清液中的激活素A。通过³H-胸腺嘧啶核苷掺入法和MTT法测定FLS的细胞生长。
免疫组织化学分析证实，与骨关节炎或正常关节组织相比，类风湿滑膜中激活素A上调。CD68+巨噬细胞系细胞和波形蛋白阳性的FLS被确定为类风湿滑膜中产生激活素的细胞。这两种细胞类型也表达ARII。在蛋白质和信使RNA水平上证实了培养的FLS上激活素A和ARII的表达。白细胞介素-1β（IL-1β）、肿瘤坏死因子α和转化生长因子β激活FLS分泌激活素A。重组激活素A加速了FLS的增殖，而内源性激活素拮抗剂卵泡抑素部分抑制了IL-1β诱导的FLS增殖。
这些结果表明激活素A在RA中作为FLS的生长因子发挥作用。
