Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients.
Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients.
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新型抗风湿药物 T-614 对类风湿关节炎患者滑膜成纤维细胞中 IL-6 诱导的 RANKL/OPG、IL-17 和 MMP-3 表达的抑制作用。
DOI：
10.1155/2015/214683
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发表时间：
2015
影响因子：
--
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Wei Y;Sun X;Hua M;Tan W;Wang F;Zhang M
T-614(又称伊古拉莫德)是一种新型抗风湿药物，可减轻类风湿性关节炎(RA)患者的关节炎症和关节损害，为RA提供了一种新的治疗方法。在这里，我们测试了T-614对IL-6诱导的类风湿关节炎(RASF)患者滑膜成纤维细胞中核因子κB配体受体激活剂(RANKL/OPG)、IL-17和MMP3表达的影响。T-614可降低IL-6诱导的RASF中RANKL的表达和RANKL/OPG比值。我们通过降低T-614或MTX对体外培养的RASF中RANKL和RANKL/OPG的mRNA和蛋白的表达来证实这一作用。T-614或MTX可显著降低IL-6诱导的RASF中IL-17、视黄醇相关孤儿受体C(RORC)和基质金属蛋白酶-3(MMP3)的表达。此外，T-614抑制p-ERK1/2蛋白的表达而不影响ERK1/2的表达，提示T-614调节RANKL表达的途径可能是ERK1/2途径。我们的结果表明，T-614通过精确抑制RANKL/OPG、IL-17和MMP3在RASF中的表达，对关节炎有明显的改善作用。
T-614 (also named as iguratimod), a novel antirheumatic drug, could attenuate joint inflammation and articular damage in rheumatoid arthritis (RA) patients, providing a new therapy for RA. Here, we tested the role T-614 on the IL-6-induced receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG), IL-17, and MMP-3 expression in synovial fibroblasts from rheumatoid arthritis (RASFs) patients. T-614 decreased RANKL expression and RANKL/OPG ratio in IL-6-induced RASFs. We confirmed this effect by a decrease of the mRNA and protein RANKL and mRNA RANKL/OPG in RASFs exposed in vitro to T-614 or MTX. Markedly decreased levels of IL-17, retinoid-related orphan receptor C (RORc), and MMP-3 mRNA expression were also observed in IL-6-induced RASFs in the presence of T-614 or MTX compared with those in its absence. Furthermore, T-614 blocked expression of p-ERK1/2 protein without affecting ERK1/2 expression, indicating that the way that T-614 regulated RANKL expression might be ERK1/2 pathway. Our results suggest that T-614 yields a strong improvement in arthritis via exact suppression of RANKL/OPG, IL-17, and MMP-3 expression in RASFs.