Selective regulation of IKKβ/NF-κB pathway involved in proliferation inhibition of HFLS-RA cells induced by 1,7-dihydroxyl-3,4-dimethoxylxanthone

作者：Ji, Cong-Lan; Jiang, Hui; Tao, Meng-Qing; Wu, Wei-Ting; Jiang, Jia; Zuo, Jian^*

来源：The Kaohsiung Journal of Medical Sciences, 2017, 33(10): 486-495.

DOI：10.1016/j.kjms.2017.06.015

• Fibroblast-like
• synoviocytes
• p65
• Rheumatoid arthritis
• Securidaca inappendiculata
• Xanthones

Rheumatoid arthritis is a common autoimmune disease, however, available regimes exert little influence on it's long-term prognosis. The aim of the current study is to investigate potential effects of 1,7-dihydroxyl-3,4-dimethoxyl-xanthone (XAN) in HFLS-RA cells and describe the underlying mechanisms of induction of NF-kappa B activity. Viability of cells was measured by MTT assay. Flow cytometry was employed to assess the pro-apoptotic effects. Modulation on NF-kB signaling was investigated by RT-qPCR, Western-blot and immunofluorescence methods. It was found that XAN induced proliferation inhibition and apoptosis of HFLSRA cells in the concentration-dependent manner, which were strengthened by pyrrolidinedithiocarbamic acid but antagonized by IKK16. NF-kappa B signaling was abrogated shortly after the treatment of XAN via various means including mRNA expression, phosphorylation and nuclear translocation, which leaded to up-regulation of p38 and down-regulation of X-linked inhibitor of apoptosis protein. Simultaneous suppressions on p-IKKb, p-IkB and p-p65 suggested the regulation on NF-kappa B was IKK beta mediated. Meanwhile, XAN promoted the expression of IKK alpha, which has a possible connection to pro-apoptotic effects suggested by the up-regulated cleaved PARP. These findings indicated IKK beta/NF-kappa B mediates the proliferation of HFLS-RA cells inhibited by XAN, and divergent regulations on IKKs could provide synergic effects on the cells' proliferation.

• 出版日期2017-10
• 单位皖南医学院; 安徽中医药大学