Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China.
Department of Obstetrics, Changchun Obstetrics-Gynecology Hospital, Changchun, Jilin, P.R. China.
J Cell Biochem. 2019 Sep;120(9):16254-16263. doi: 10.1002/jcb.28906. Epub 2019 May 14.
Rheumatoid arthritis (RA) is an autoimmune disease of the joints characterized by synovial hyperplasia and chronic inflammation. Fibroblasts-like synoviocytes (FLS), major cells in the synovium, together with infiltrated leukocytes, contribute greatly to RA progression. In our study, we hypothesized that geldanamycin (GA), a cancer drug might be able to inhibit RA FLS growth. To test the idea, RA FLS were isolated and cultured for cancer drug test. The results showed that GA can specifically inhibit the growth of RA FLS compared with normal FLS. Essentially, GA was found to promote reactive oxygen species production in RA FLS and induce programmed cell death. The annexinV/propidium iodide and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining confirmed that GA can directly induce apoptosis and subsequently inhibit the growth of RA FLS, which was also confirmed by Western blot assay. In addition, our data demonstrated that inflammation was inhibited by suppressed nuclear factor κB signaling pathway. The therapeutic effect of GA was explored in collagen-induced arthritis mice. In short, GA was a promising drug for the treatment of RA by specifically inhibiting the proliferation and inflammation of RA FLS.
类风湿关节炎（RA）是一种以滑膜增生和慢性炎症为特征的关节自身免疫性疾病。成纤维样滑膜细胞（FLS）是滑膜中的主要细胞，与浸润的白细胞一起，对 RA 的进展有很大的贡献。在我们的研究中，我们假设格尔德霉素（GA），一种癌症药物，可能能够抑制 RA FLS 的生长。为了验证这一想法，我们分离并培养 RA FLS 进行癌症药物测试。结果表明，GA 可以特异性地抑制 RA FLS 的生长，而对正常 FLS 没有影响。本质上，GA 被发现可以促进 RA FLS 中活性氧的产生，并诱导程序性细胞死亡。AnnexinV/碘化丙啶和末端脱氧核苷酸转移酶 dUTP 缺口末端标记染色证实 GA 可以直接诱导细胞凋亡，随后抑制 RA FLS 的生长，这也通过 Western blot 检测得到了证实。此外，我们的数据表明，炎症被抑制的核因子 κB 信号通路。GA 在胶原诱导性关节炎小鼠中的治疗效果也进行了探索。总之，GA 通过特异性抑制 RA FLS 的增殖和炎症，是一种有前途的治疗 RA 的药物。
