Increased multidrug resistance-associated protein activity in mononuclear cells of patients with systemic lupus erythematosus.
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 MRP1, MRP2, and MRP3 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 MRP1, MRP2, and MRP3 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.
Lu
M-C
MC
Division of Immunology, Rheumatology and Allergy, Buddhist DaLin Tzu-Chi General Hospital, Chia-Yi, Taiwan.
Lai
N-S
NS
Li
K-J
KJ
Hsieh
S-C
SC
Wu
C-H
CH
Yu
C-L
CL
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000493:pharmacokinetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D012235:Rhodamines / Q000493:pharmacokinetics; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D008942:Mitoxantrone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012235:Rhodamines