Role of NF-κB signaling pathway in methotrexate resistance of patients with rheumatoid arthritis

YAO Xueming; LIANG Shuang; MA Wukai; NING Qiaoyi; ZHONG Qin; HOU Lei; HUANG Ying; TANG Fang

doi:10.3969/j.issn.1002-266X.2017.14.007

Abstract：Objective To investigate the role of nuclear factor-κB (NF-κB) signaling pathway in the mechanisms of methotrexate (MTX) resistance of patients with rheumatoid arthritis (RA).Methods Totally 120 RA patients taking MTX were selected and were divided into MTX sensitive group and MTX resistant group according to their joint disease activity (DAS28) score,and another 20 healthy volunteers were chosen as the normal control group.ELISA was used to detect the levels of NF-κB,inhibitory protein IκBα (IκBα),TNF-α and IL-1β in serum of each group.The expression of multidrug resistance gene 1 (MDR1),TNF-α and IL-1β mRNA in the MTX sensitive group and MTX resistant group was detected by fluorescence PCR.Flow cytometry was used to detect the expression and function of P glycoprotein (P-gp) in the peripheral blood mononuclear cells (PBMCs).Results The levels of NF-κB,TNF-α and IL-1β in the MTX sensitive group and MTX resistant group were higher,and the IκBα levels were lower than those of the normal control group (all P<0.05).The levels of NF-κB,TNF-α and IL-1β in the MTX resistant group were higher than those in the MTX sensitive group,and the level of IκBα was lower than that of the MTX sensitive group (all P<0.05).The expression of MDR1,TNF-α and IL-1β mRNA in the MTX resistant group were higher than those in the MTX sensitive group (all P<0.05).The P-gp fluorescence value of the MTX sensitive group and MTX resistant group was higher than that of normal control group,and Rh123 fluorescence value was lower than that of normal control group (both P<0.05).The P-gp value of the MTX resistant group was higher than that in the MTX sensitive group,and the fluorescence value of Rh123 was lower than that of the MTX sensitive group (both P<0.05).Conclusion The expression of MDR1 was increased in RA patients after MTX resistance,and the mechanism of multidrug resistance was related to activation of NF-κB signaling pathway.