Hayat Faisal, Lee Seung Hoon, Lee Eun-Jung, Kim Seok Jung, Jung KyungAh, Lee Soon Kyu, Youn Jeehee, Min Jun-Ki, Cho Mi-La, Shin Dong-Yun
1College of Pharmacy, Gachon University, Seoul, Korea.
2The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea.
Tissue Eng Regen Med. 2016 Feb 2;13(1):91-99. doi: 10.1007/s13770-016-9086-0. eCollection 2016 Feb.
Rheumatoid arthritis (RA) is an autoimmune disease with chronic and excessive inflammation. Upregulation of interleukin (IL)-17 is involved in the pathogenesis of RA. STX0119 is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) as a potential target for the treatment of RA. STAT3 is a member of DNA-binding molecules that regulates the expression of proinflammatory cytokines involved in the pathogenesis of RA. The objective of this study was to determine whether STX0119 could inhibit STAT3 and IL-17. We demonstrated that STX0119 decreased T helper (Th) 17 differentiation and IL-17 expression . STX0119 also improved the severity of zymosan induced arthritis and reduced joint inflammation. STX0119 reduced the proliferation of Th17 and phosphorylated STAT3 expression while increasing Treg differentiation and phosphorylated STAT5 expression. Moreover, STX0119 decreased the expression of IL-6 and -17 but not IL-10. These findings suggest that STX0119 can be used to treat autoimmune RA through inhibiting the activation of STAT3.
类风湿关节炎(RA)是一种伴有慢性过度炎症的自身免疫性疾病。白细胞介素(IL)-17的上调参与了RA的发病机制。STX0119是信号转导和转录激活因子3(STAT3)的特异性抑制剂,作为治疗RA的潜在靶点。STAT3是DNA结合分子的成员,可调节参与RA发病机制的促炎细胞因子的表达。本研究的目的是确定STX0119是否能抑制STAT3和IL-17。我们证明STX0119可降低辅助性T细胞(Th)17分化和IL-17表达。STX0119还改善了酵母聚糖诱导的关节炎的严重程度并减轻了关节炎症。STX0119减少了Th17的增殖和磷酸化STAT3的表达,同时增加了调节性T细胞(Treg)的分化和磷酸化STAT5的表达。此外,STX0119降低了IL-6和IL-17的表达,但未降低IL-10的表达。这些发现表明,STX0119可通过抑制STAT3的激活来治疗自身免疫性RA。