P-glycoprotein in autoimmune diseases.
Multidrug resistance-1 (MDR-1) is characterized by overfunction of P-glycoprotein (P-gp), a pump molecule that decreases intracellular drug concentration by effluxing them from the intracellular space. Broad ranges of structurally unrelated compounds are transported by P-gp, including antineoplastic agents, HIV protease inhibitors, prednisone, gold salts, methotrexate, colchicine as well as several antibiotics. In contrast, many other compounds such as calcium channel blockers (verapamil) and immunosupressors (cyclosporine-A) are able to inhibit P-gp function. The P-gp role in therapeutic failures has been extensively studied in cancer; however, there is little information regarding MDR-1 phenotype in autoimmune disorders. It has been reported that an increased number of lymphocytes are able to extrude P-gp substrates in rheumatoid arthritis, immune thrombocytopenic purpura and systemic lupus erythematosus, the patients with poor response to treatment being the ones that exhibit the highest values. This may be due, at least in part, to a simultaneous long-term usage of several drugs that induce P-gp function. Since abnormally activated cell compartments characterize autoimmune diseases, it is possible that those cells are the ones that exhibit drug resistance. The study of drug resistance mechanisms in autoimmunity may be helpful for the optimization of the current therapeutic schemes through their combination with low doses of P-gp inhibitors.
Richaud-Patin
Yvonne
Y
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Tlalpan, 14000 Mexico City, Mexico.
Soto-Vega
Elena
E
Jakez-Ocampo
Juan
J
Llorente
Luis
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D017320:HIV Protease Inhibitors; D007166:Immunosuppressive Agents