Increased multidrug resistance-associated protein activity in mononuclear cells of patients with systemic lupus erythematosus

CER3351
2008 Vol.26, N°4
PI 0638, PF 0645
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PMID: 18799096 [PubMed]

Abstract

ABSTRACT:Multidrug resistance-associated proteins (MRPs, ATP binding cassette sub-family C), P-glycoprotein (P-gp) and ATP binding cassette (ABC) sub-family G member 2 (ABCG2) are important drug efflux pumps emerging after long-term medications. We intended to detect whether these molecules are expressed in immune-related cells of patients with systemic lupus erythematosus (SLE) on long-term immunosuppressants.
METHODS:
Mono nuclear cells (MNC) and polymorphonuclear neutrophils (PMN) were isolated from healthy volunteers and SLE patients. The MPR-mediated transport activity of these cells was measured by using carboxy-2`,7`-dichlorofluorescein diacetate (CFDA) efflux assay. P-gp-mediated transport activity of cells was detected by rhodamine 123 efflux assay. ABCG2-mediated transport assay was evaluated by mitoxantrone efflux assay. The intracellular expression of MRP<inf>1</inf>, MRP<inf>2</inf>, and MRP<inf>3</inf> molecules in MNC was detected by flow cytometry. The results were compared between MNC and PMN derived from normal and SLE groups.
RESULTS:
The specific dye-efflux function of MRPs in SLE-MNC is significantly higher than normal MNC. However, the expression of MRP<inf>1</inf>, MRP<inf>2</inf>, and MRP<inf>3</inf> molecules in SLE-MNC was not different from normal MNC. We also noted that only the duration of corticosteroid treatment in different clinical/laboratory parameters was significantly correlated with the increased activity of MRPs in SLE-MNC.
CONCLUSIONS:
These results suggest that increased activity of MRPs in SLE-MNC is elicited by long-term corticosteroid therapy.