Piperlongumine inhibits the proliferation, migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis
Piperlongumine inhibits the proliferation, migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis
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Piperlongumine 抑制类风湿关节炎患者成纤维细胞样滑膜细胞的增殖、迁移和侵袭
DOI：
10.1007/s00011-017-1112-9
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发表时间：
2018-03-01
影响因子：
6.7
通讯作者：
Xu, Hanshi
中科院分区：
文献类型：
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作者：
Xu, Siqi;Xiao, Youjun;Xu, Hanshi
目的最近的研究表明胡椒长明 (PLM) 可能具有抗炎作用。在本研究中，我们确定了PLM对类风湿性关节炎（RA）患者的成纤维样滑膜细胞（FLS）（本文称为RA FLS）的增殖、凋亡、迁移和侵袭的影响。我们进一步探讨了所研究的化合物抑制RA FLS功能的机制。方法分别使用MTT和Annexin V/PI测定法测试RA FLS活力和细胞凋亡。我们进行了 EDU 测定来检查 RA FLS 的增殖。使用transwell小室方法和伤口闭合测定来测量这些细胞的迁移和侵袭。使用Luminex Assay试剂盒检测RA FLS培养上清液中的MMP-1、MMP-3和MMP-13水平。使用DCFH-DA检测细胞内ROS水平。使用蛋白质印迹测量信号转导蛋白的表达水平。结果我们发现PLM在15和20μM浓度下诱导RA FLS细胞凋亡。 1、5 和 10 μM 浓度的 PLM 下调 RA FLS 的增殖。浓度为 1、5 和 10 μM 的 PLM 可减少 RA FLS 的迁移和侵袭。 PLM 还抑制迁移 RA FLS 中的细胞骨架重组，并减少 TNF-α 诱导的细胞内 ROS 产生。此外，我们证明了PLM对p38、JNK、NF-κB和STAT3通路激活的抑制作用。结论我们的研究结果表明PLM可以抑制RA FLS的增殖、迁移和侵袭。此外，这些数据表明 PLM 可能具有治疗 RA 的潜力。
ObjectivesRecent studies have indicated that piperlongumine (PLM) may exert anti-inflammatory effects. In the present study, we determined the effect of PLM on the proliferation, apoptosis, migration and invasion of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) (referred to herein as RA FLS). We further explored the mechanisms by which the studied compound inhibits the functions of RA FLS.MethodsRA FLS viability and apoptosis were tested using MTT and Annexin V/PI assays, respectively. We performed an EDU assay to examine the proliferation of RA FLS. The migration and invasion of these cells were measured using a transwell chamber method and wound closure assay. The MMP-1, MMP-3, and MMP-13 levels in the culture supernatants of RA FLS were detected using a Luminex Assay kit. The intracellular ROS levels were detected using DCFH-DA. The expression levels of signal transduction proteins were measured using western blot.ResultsWe found that PLM induced apoptosis in RA FLS at concentrations of 15 and 20 μM. The proliferation of RA FLS was downregulated by PLM at concentrations of 1, 5 and 10 μM. Migration and invasion of RA FLS were reduced by PLM at concentrations of 1, 5 and 10 μM. PLM also inhibited cytoskeletal reorganization in migrating RA FLS and decreased TNF-α-induced intracellular ROS production. Moreover, we demonstrated the inhibitory effect of PLM on activation of the p38, JNK, NF-κB and STAT3 pathways.ConclusionsOur findings suggest that PLM can inhibit proliferation, migration and invasion of RA FLS. Moreover, these data suggests that PLM might have therapeutic potential for the treatment of RA.