Selective regulation of IKKβ/NF‐κB pathway involved in proliferation inhibition of HFLS‐RA cells induced by 1,7‐dihydroxyl‐3,4‐dimethoxylxanthone
Open Access
- 13 July 2017
- journal article
- Published by Wiley in The Kaohsiung Journal of Medical Sciences
- Vol. 33 (10), 486-495
- https://doi.org/10.1016/j.kjms.2017.06.015
Abstract
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-κB activity. Viability of cells was measured by MTT assay. Flow cytometry was employed to assess the pro-apoptotic effects. Modulation on NF-κB signaling was investigated by RT-qPCR, Western-blot and immunofluorescence methods. It was found that XAN induced proliferation inhibition and apoptosis of HFLS-RA cells in the concentration-dependent manner, which were strengthened by pyrrolidinedithiocarbamic acid but antagonized by IKK16. NF-κB 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-IKKβ, p-IκB and p-p65 suggested the regulation on NF-κB was IKKβ mediated. Meanwhile, XAN promoted the expression of IKKα, which has a possible connection to pro-apoptotic effects suggested by the up-regulated cleaved PARP. These findings indicated IKKβ/NF-κB mediates the proliferation of HFLS-RA cells inhibited by XAN, and divergent regulations on IKKs could provide synergic effects on the cells' proliferation.Keywords
Funding Information
- National Natural Science Foundation of China (81603388)
- Natural Science Foundation of Anhui Province (1508085SQH226)
- National Natural Science Foundation of China (81603388)
- Natural Science Foundation of Anhui Province (1508085SQH226)
- 2016 Key Project of Natural Science Foundation of Anhui Province (KJ2016A419)
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