The effects of DMARDs on the expression and function of P-gp, MRPs, BCRP in the treatment of autoimmune diseases

Publication date: September 2018
Source:Biomedicine & Pharmacotherapy, Volume 105
Author(s): Yi-jin Wu, Chun Wang, Wei Wei
The ATP-binding cassette (ABC) transporter family is a large class of ATP energy-dependent transmembrane proteins, and its primary function is to use the energy produced by ATP hydrolysis to transfer the substrate bound to the plasma membrane. This family is also closely related to multidrug resistance (MDR) in various diseases. Among the ABC transporter proteins, P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP) are the main members associated with MDR. At present, the roles of these transporters in therapeutic failures have been extensively studied and reviewed in cancer; however, they have rarely been described in autoimmune diseases (AIDs). AID is a group of chronic inflammatory diseases of unknown aetiology. AID's basic feature is the production of a large number of autoantibodies, which leads to extensive damage to multiple systems and multiple organs. Disease-modifying anti-rheumatic drugs (DMARDs) are commonly used in the treatment of AID, but a considerable number of patients have no response or develop resistance to these drugs over time. This phenomenon may be related to the abnormal expression of the ABC transporter, which leads to a decrease in the amount of drug entering cells that produce MDR. This article reviews the effects of DMARDs on the expression and function of P-gp, MRPs, and BCRP and the related molecular mechanism in the treatment of AID.

Graphical abstract

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