Activin a induces cell proliferation of fibroblast-like synoviocytes in rheumatoid arthritis
Activin a induces cell proliferation of fibroblast-like synoviocytes in rheumatoid arthritis
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DOI：
10.1002/art.11249
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发表时间：
2003-09-01
影响因子：
--
通讯作者：
Nojima, Y
中科院分区：
文献类型：
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作者：
Ota, F;Maeshima, A;Nojima, Y
客观的。探讨激活素A及其受体在类风湿性关节炎(RA)滑膜组织中的表达，并探讨激活素A对培养的成纤维样滑膜细胞(FLS)的影响。方法。通过免疫组织化学分析 RA 患者滑膜组织中激活素 A 和激活素 II 型受体 (ARII) 的定位。采用逆转录酶-聚合酶链式反应和Western blotting检测人培养FLS中激活素A和激活素受体的表达，酶联免疫吸附法测定培养上清液中激活素A。通过H-3-胸苷掺入和MTT法测定FLS的细胞生长。结果。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 的表达上调。 CD68+巨噬细胞谱系细胞和波形蛋白阳性FLS被鉴定为类风湿滑膜中产生激活素的细胞。两种细胞类型都表达 ARII。激活素 A 和 ARII 在培养的 FLS 上的表达在蛋白质和信使 RNA 水平上得到了证实。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FLS的增殖，而内源性激活素拮抗剂卵泡抑素部分抑制IL-1β诱导的FLS增殖。结论。这些结果表明激活素 A 在 RA 中充当 FLS 的生长因子。
Objective. 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).Methods. 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 H-3-thymidine incorporation and MTT assay.Results. 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-1beta (IL-1beta), 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-1beta.Conclusion. These results suggest that activin A acts as a growth factor of FLS in RA.