Open AccessSelective regulation of IKKβ/NF‐κB pathway involved in proliferation inhibition of HFLS‐RA cells induced by 1,7‐dihydroxyl‐3,4‐dimethoxylxanthone
Author(s) -
Ji CongLan,
Jiang Hui,
Tao MengQing,
Wu WeiTing,
Jiang Jia,
Zuo Jian
Publication year - 2017
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2017.06.015
Subject(s) - apoptosis , flow cytometry , nf κb , medicine , western blot , phosphorylation , signal transduction , cancer research , iκbα , mtt assay , viability assay , iκb kinase , microbiology and biotechnology , immunology , biology , biochemistry , gene
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.