Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid arthritis

Abstract

The main purpose of treatment of rheumatoid arthritis

Methotrexate Combined with 4-Hydroperoxycyclophosphamide Downregulates Multidrug-Resistance P-Glycoprotein Expression Induced by Methotrexate in Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the JAK2/STAT3 Pathway

“…P-gp reacts differently to the three types of substrate [ 31 ]. Controversy remains as to whether MTX is a complete substrate for P-gp, with some studies suggesting it is [ 7 , 28 ], and others arguing that it is not [ 31 ]; nevertheless, it is clear that MTX has an obvious effect on P-gp [ 8 – 10 ]. The interaction between MTX and P-gp may involve factors in addition to the efflux pump.…”

“…In addition to serving as the primary treatment for RA, MTX is a specific substrate of P-gp [ 7 ]. Several studies have demonstrated P-gp overexpression in the lymphocytes or synovial cells of MTX-resistant RA patients [ 8 – 10 ]. Treatment with the P-gp inhibitors, cyclosporine A and tacrolimus, has been shown to significantly improve the clinical symptoms and laboratory indicators in RRA patients [ 11 , 12 ].…”

Effect of ultraviolet irradiation on free radical scavenging activity of immunosuppressants used in lung transplantation and comparative electron paramagnetic resonance study of kinetics of their interactions with model free radicals

“…The mechanism of action of immunosuppressants is well defined. Calcineurin inhibitors (ciclosporin), mTor inhibitors (sirolimus alternative name rapamycin) and cell cycle blockers (mycophenolate mofetil) have been used widely for many years in the treatment of various diseases such as scleroderma, multiple sclerosis, lupus erythematosus and rheumatoid arthritis, with significant efficacy …”

Immunotherapeutic Approaches of Rheumatoid Arthritis and the Implication on Novel Interventions for Refractoriness

“…P-glycoprotein (P-gp)-mediated drug resistance P-gp, also known as multidrug resistance protein 1 (MDR1) or CD243, is an important membrane pumps for the cellular removal of foreign substances. In patients with refractory RA and high disease activity, overexpression of P-gp on lymphocytes can cause resistance to antirheumatic drugs through efflux of intracellular drugs [134]. Recent studies further showed that high expression level of P-gp found in FLS of refractory RA patients is the potential mechanism for multidrug resistance in RA treatment [135].…”