青蒿琥酯对类风湿关节炎滑膜细胞TNF-α分泌的抑制作用及其机制研究

Artesunate inhibits LPS-induced production of TNF-α via inhibition of NF-κB signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes

目的研究青蒿素衍生物青蒿琥酯对类风湿关节炎(RA)滑膜细胞(FLS)分泌肿瘤坏死因子(TNF)-α的影响,并进一步探讨其机制。方法来自活动性RA患者的FLS用脂多糖(LPS)刺激和青蒿琥酯处理,TNF-α水平用酶联免疫吸附试验(ELISA)测定,核因子(NF)-κB活性检测采用电泳迁移率改变试验(EMSA)。结果青蒿琥酯显著抑制LPS诱导的TNF-α分泌,并且呈剂量依赖性。青蒿琥酯对LPS刺激的NF-κB活化有明显抑制作用,NF-κB抑制剂二硫代氨基吡咯烷(PDTC)亦显著抑制LPS刺激的滑膜细胞分泌TNF-α。结论青蒿琥酯通过调节NF-κB活性抑制LPS诱导的RA滑膜细胞分泌TNF-α,提示青蒿琥酯可能具有抑制RA滑膜炎症的作用。

Objective Recent studies have indicate that the anti-malarial artemisinin and its derivatives may exert anti-inflammatory and immunomodulatory effects. In this study, we explored the effect of artesunate, a artemisinin derivative, on LPS-induced production of TNF-α in human rheumatoid arthritis （RA） fibroblast-like synoviocytes （FLS）, and further investigated the signal mechanism by which this compound modulates the cytokine production. Methods RA FLS obtained from patients with active rheumatoid arthritis were stimulated with LPS and incubated with artesunate. TNF-α production was measured by ELISA and DNA-binding activity of NF-κB was measured by EMSA. Results Artesunate decreased the secretion of TNF-α from LPS-stimulated RA FLS in a dose-dependent manner, and also suppressed LPS-α-induced NF-κB DNA-binding activity. The production of TNF-α induced by LPS was decreased by PDTC, a chemical inhibitor of NF-κB. These observations suggest that artesunate inhibits production of TNF-α through inhibition of NF-κB signaling pathway. Conclusion Our results indicated that artesunate exert anti-inflammatory effect in RA FES and provided evidence of artesunate as a potential treatment for RA.