Multidrug resistance proteins in rheumatoid arthritis, role in disease-modifying antirheumatic drug efficacy and inflammatory processes: an overview.
Drug resistance is generally accepted as an important cause of treatment failure for patients with neoplastic or infectious diseases. Molecular mechanisms underlying drug resistance include the action of drug efflux pumps belonging to the super-family of ATP binding cassette (ABC) proteins, which mediate the cellular extrusion of a large variety of therapeutic drugs, a phenotype that is referred to as multidrug resistance (MDR). Unlike neoplastic and infectious diseases, chronic inflammatory diseases have received little attention. The potential role of ABC transporters in determining the efficacy of anti-rheumatic drugs, notably disease modifying anti-rheumatic drugs (DMARDs), in patients with rheumatoid arthritis is unclear. Based on knowledge from the field of oncology and immunology, this review concentrates on the pharmacological role of MDR proteins in the (clinical) efficacy of several DMARDs, as well as the physiological role of MDR proteins in transporting signalling molecules important in inflammatory processes.
Jansen
G
G
Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. g.jansen@vumc.nl
Scheper
R J
RJ
Dijkmans
B A C
BA
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects* / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000187:drug effects; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000378:metabolism; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D001682:Biological Availability; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D008297:Male; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015854:Up-Regulation
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D018501:Antirheumatic Agents; D018836:Inflammation Mediators