The expression of multidrug resistance gene 1 and P-glycoprotein in peripheral blood lymphocytes of patients with steroid resistant systemic lupus erythematosus
WANG Meiying
ZENG Peiying
ZHOU Gengmin
LYU Jiyang
ZHU Yisheng
CHEN Cheng
WANG Qingwen
GUO Chengshan
Abstract：This study was performed to investigate the expression of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp) in peripheral lymphocytes from systemic lupus erythematosus patients with poor responses to systemic steroid therapy.A total of 60 SLE patients who had received systemic steroid treatment for longer than 6 months and 30 healthy subjects were monitored.SLE patients were subclassified into those with steroid-effective group (n=49) and steroid-resistant group (n=1 1) according to their disease activity (estimated by SLEDAI-2000)after treatment.RT-PCR was used to detect the expression of MDR1 mRNA,the flow cytometry was used to detect the P-gp expression,and rhodamine 123 was used to detect the P-gp activity.Lymphocytes,obtained from 11 patients with steroid-resistant SLE,with high levels of P-gp expression were treated with cyclophosphamide,mycophenolic acid or Tariquidar in vitro,and subjected to measure Rh123-efflux activity.Data showed that,after 6 months of treatment,the expression of MDR1 mRNA and the expression and activity of P-pg from patients with steroid-resistant group were significantly higher than steroid-effective group and healthy controls.Treatment of lymphocytes with 100 μmol/L cyclophosphamide or 100 μmol/L Tariquidar in vitro induced up to a 2-fold increase in the mean fluorescence intensity,as detected by the Rh123-efflux assay.In conclusion,the high expression levels of MDR1 mRNA and P-gp in the peripheral lymphocytes of SLE patients lead to poor disease control by systemic steroids.CTX,as a special type of P-Glycoprotein inhibitor,possesses a promising effect for overcoming P-gp-mediated steroid resistance by inhibiting the P-gp activity.
Keywords：Multidrug resistanceP-glycoproteinSystemic lupus erythematosusSteroid resistanceCyclophosphamide
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 1053-1059 )