Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis
Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis
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氯硝柳胺对类风湿性关节炎成纤维样滑膜细胞炎症和迁移的抑制作用
DOI：
10.1007/s00011-015-0801-5
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发表时间：
2015-04-01
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：
Liang, Liuqin;Huang, Mingcheng;Xu, Hanshi
本研究评价了氯硝柳胺对肿瘤坏死因子（TNF）-α刺激的人类风湿关节炎（RA）成纤维样滑膜细胞（FLS）的抗炎作用和对RA FLS迁移和侵袭的抑制作用，并探讨了其信号机制，进一步探讨了氯硝柳胺对胶原诱导的关节炎（CIA）的治疗活性。通过多重细胞因子测定试剂盒测量培养上清液中的IL-10、IL-17 A和干扰素（IFN）-γ。用Boyden小室法和划痕法检测RA FLS的体外迁移和侵袭能力。Western blot检测细胞内信号转导蛋白的表达。氯硝柳胺在小鼠模型中对CIA的体内抑制作用得以阐明。氯硝柳胺以剂量依赖性方式减少TNF-α诱导的RA FLS中IL-1 β、IL-6、IL-8、IL-17 A和IFN-γ的分泌。氯硝柳胺抑制FBS诱导的迁移和侵袭，并在RA FLS中表现出F-肌动蛋白改变。氯硝柳胺降低TNF-α刺激的RA FLS中c-Jun N-末端激酶和ERK的磷酸化，并阻断TNF-α诱导的IKK、I κ B α磷酸化和p65易位。氯硝柳胺治疗可减轻CIA模型的严重程度，我们的数据首次表明氯硝柳胺在体外和体内均对RA具有抗炎作用。
This study evaluated the anti-inflammatory effect of niclosamide in tumor necrosis factor (TNF)-alpha-stimulated human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and inhibitory effects on migration and invasion in RA FLS and investigated the signal mechanism, and further explored the treatment activity of niclosamide on collagen-induced arthritis (CIA).The levels of interleukin (IL)-1 beta, IL-6, IL-8, IL-10,IL-17A and interferon (IFN)-gamma in cultural supernatants were measured by multiplex cytokine assay kits. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction proteins expression was measured by western blot. The in vivo suppressive effects of niclosamide were elucidated on CIA in a mouse model.Niclosamide reduced the secretion of IL-1 beta, IL-6, IL-8, IL-17A and IFN-gamma from TNF-alpha-induced RA FLS in a dose-dependent manner. Niclosamide inhibits FBS-induced migration and invasion and exhibits F-actin alterations in RA FLS. Niclosamide decreased the phosphorylation of c-Jun N-terminal kinase and ERK in TNF-alpha-stimulated RA FLS and blocked TNF-alpha-induced IKK, I kappa B alpha phosphorylation and translocation of p65. Niclosamide treatments reduced the severity of CIA model.Our data suggest for the first time that niclosamide posses the anti-inflammatory effect in RA both in vitro and in vivo.