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首页> 外文期刊>International immunopharmacology >Amelioration of collagen antibody induced arthritis in mice by an antibody directed against the fibronectin type III repeats of tenascin-C Targeting fibronectin type III repeats of tenascin-C in rheumatoid arthritis
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Amelioration of collagen antibody induced arthritis in mice by an antibody directed against the fibronectin type III repeats of tenascin-C Targeting fibronectin type III repeats of tenascin-C in rheumatoid arthritis

机译：通过针对类纤维蛋白-c靶向纤维蛋白-c靶向纤维蛋白-c的纤连蛋白-c重复的纤维连接蛋白III重复的纤连蛋白-c的纤连蛋白-c靶向纤维蛋白-c重复的抗体诱导的关节炎。

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Tenascin-C (TN-C) levels are elevated in the synovial tissue and fluid, as well as cartilage of rheumatoid arthritis (RA) patients. In addition, the presence of TN-C fragments has also been documented in arthritic cartilage. We have previously shown that a single chain variable fragment antibody (TN64), directed against the fibronectin type III repeats 1-5 (TNfnIII 1-5) of TN-C, effectively inhibits fibrotic pathology. Given that fibrosis results from chronic inflammation, and the fact that increased levels of TN-C in the synovial fluid of patients with RA contributes to synovial inflammation and joint destruction, we aimed to investigate the role of TNfnIII 1-5 region of TN-C in RA pathogenesis. Using either the wild type or variants of the two integrin-binding motifs (RGD and AEIDGIEL) present within the TNfnIII 1-5 polypeptide, we demonstrate that the adhesion and migration of synovial fibroblasts is RGD-dependent. The antibody TN64 is effective in inhibiting migration of cells in response to TnfnIII 1-5, and prevents fibroblast-mediated destruction of cartilage. The TN64 antibody was further tested in collagen antibody induced arthritic (CAIA) mice. Our data shows the efficacy of TN64 in preventing induction of arthritis, with significant downregulation of RA-associated cytokines. This suggests that components of the extracellular matrix such as the TNfnIII 1-5 region of TN-C could be exploited to develop therapies to suppress inflammation seen in RA. The TN64 antibody is one such promising candidate in the development of novel treatments for RA.
机译：在滑膜组织和液体中升高Tenascin-C（TN-C）水平，以及类风湿性关节炎（RA）患者的软骨。此外，在关节炎软骨中还记录了TN-C片段的存在。我们之前已经表明，针对纤连蛋白III型III的单链可变片段抗体（TN64）重复1-5（TNFNII 1-5）的TN-C，有效抑制纤维化病理学。鉴于纤维化来自慢性炎症的纤维化，以及RA患者的滑膜中TN-C水平增加的事实有助于滑膜炎症和联合破坏，我们旨在调查TNFNIII 1-5 TN-C区域的作用在RA发病机制中。使用存在于TNFNIII 1-5多肽内的两种整联蛋白结合基序（RGD和Aeidgiel）的野生型或变体，我们证明了滑膜成纤维细胞的粘附和迁移是RGD依赖性的。抗体TN64有效地抑制细胞的迁移响应于TNFNIII 1-5，并防止成纤维细胞介导的软骨破坏。在胶原抗体诱导的关节炎（CAIA）小鼠中进一步测试TN64抗体。我们的数据显示TN64在预防关节炎的诱导方面的疗效，具有显着的RA相关细胞因子的下调。这表明细胞外基质的组分如TNFNIII 1-5区域的TN-C区域可以被利用，以开发抑制RA中所见的炎症的疗法。 TN64抗体是在对RA的新方法的发展中进行的一个如此有希望的候选者。

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