Publication: Relevance of multidrug resistance 1 and P-glycoprotein to drug resistance in patients with systemic lupus erythematosus
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Date
2007
Authors
Tsujimura, S. ; Saito, K. ; Nakayamada, S. ; Tanaka, Y.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Although corticosteroids and immunosuppressants
are widely used for the treatments of
various autoimmune diseases such as systemic lupus
erythematosus (SLE), we often experience patients with
SLE who are resistant to these treatments. Pglycoprotein
(P-gp) of membrane transporters, a product
of the multiple drug resistance (MDR)-1 gene, is known
to play a pivotal role in the acquisition of drug resistance
to chemotherapies in malignancy. However, the
relevance of MDR-1 and P-gp to resting and activated
lymphocyte, major targets of the treatments in
autoimmune diseases, remains unclear. We found that
peripheral lymphocytes in patients with SLE express Pgp
on the surface and its expression is highly correlated
with disease activity. P-gp on lymphocytes is induced by
not only genotoxic stresses but also activation stimuli
such as cytokines, resulting in active efflux of
corticosteroids from cytoplasm of lymphocytes, resulting
in drug-resistance and high disease activity. However,
the addition of P-gp antagonists such as ciclosporin A
and inhibitors of P-gp synthesis successfully reduce
efflux of corticosteroids from lymphocytes in vitro and
these results imply that P-gp antagonists and P-gp
synthesis inhibitors could work in order to overcome
drug-resistance in vivo. Therefore, we propose that the
measurement of P-gp on lymphocytes is a useful marker
to indicate drug resistance and requirement of
antagonists and/or intensive treatments to overcome drug
resistance in active SLE patients
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