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

Figure 2 Schematic diagram of the relevance of P-glycoprotein to drug resistance in rheumatoid arthritis. A: Y-box-binding protein-1 is located in the cytoplasm of lymphocytes and P-glycoprotein (P-gp) is only marginally expressed on normal lymphocytes of normal subjects and patients with inactive RA; B: In patients with highly active rheumatoid arthritis (RA), various stimuli induce P-gp expression on lymphocytes, which leads to active efflux of drugs from lymphocytes, resulting in drug-unresponsiveness and failure to control disease activity; C: Reduction of P-gp achieved by intensive immunosuppressive therapy and inhibition of P-gp by competitive antagonists, such as cyclosporine, could overcome P-gp-related drug-resistance in patients with highly active RA. DMARDs: Disease modifying antirheumatic drugs; MDR-1: Multidrug resistance 1.