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Detection of active P-glycoprotein in systemic lupus erythematosus patients with poor disease control.


Exp Ther Med. 2012 Oct;4(4):705-710


Authors: Zhang B, Shi Y, Lei TC


Abstract

Active P-glycoprotein (P-gp) molecules have been shown to transport steroids out of peripheral lymphocytes, resulting in poor responses to systemic steroid therapy in patients with systemic lupus erythematosus (SLE). This study was carried out to investigate the correlation between the expression or activity of P-gp in peripheral lymphocytes and disease control in SLE patients with a long history of systemic steroid treatment. 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 active and severely active forms of the disease according to their disease activity (estimated by SLEDAI-2000). The expression levels and activity of P-gp in peripheral blood lymphocytes were determined. Lymphocytes, obtained from three patients with severely active SLE, with high levels of P-gp expression were treated with cyclophosphamide, mycophenolic acid or emodin in vitro and Rh123-efflux activity was measured. P-gp expression in the peripheral lymphocytes of the SLE patients was significantly higher compared with that of the healthy controls, and a positive correlation between disease activity and P-gp expression levels was observed in these 60 patients. A significant increase in P-gp expression was observed in the severely active compared with the active SLE group. Treatment of lymphocytes with 100 μM cyclophosphamide or 100 μM emodin 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 P-gp in the peripheral lymphocytes of SLE patients leads to poor disease control by systemic steroids. Emodin, an active ingredient derived from Chinese herbs, possesses a promising effect for overcoming P-gp-mediated steroid resistance by inhibiting the P-gp efflux function.

PMID: 23170130 [PubMed - as supplied by publisher]