Overexpression of P-glycoprotein on fibroblast-like synoviocytes in refractory rheumatoid arthritis patients: a potential mechanism for multidrug resistance in rheumatoid arthritis treatment.
This study aims to investigate the role of P-glycoprotein (P-gp) expression level in drug resistance to disease-modifying anti-rheumatic drugs in refractory rheumatoid arthritis (RRA). We evaluated and compared the expression levels of P-gp in fibroblast-like synoviocyte (FLS) cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and investigated the potential mechanism of P-gp-induced multidrug resistance in RRA. Ten patients were enrolled and divided into two groups: six in the RA group and four in the OA group. The expression level of P-gp in FLS cells was detected by western blotting following cell culture. A linear correlation algorithm was used to assess the association between the level of P-gp and disease activity  (using DAS28 scoring), as well as the duration of methotrexate (MTX) treatment in the RRA patients. The level of P-gp in the RRA patients was markedly higher than that in the OA patients (P < 0.05, t = -4.179). There was a positive linear correlation between the P-gp level in FLS cells and the duration of MTX treatment in the RRA group (Г = 0.733, P < 0.05), whereas there was no significant correlation between the P-gp level and DAS28 scoring (Г = 0.206, P > 0.05). P-gp might be upregulated during the progression of RRA, which possibly correlates with the development of resistance to MTX.
Department of Rheumatology Immunology, The Second Xiangya Hospital of Central South University, Changsha.
Y M
YM
Liu
Department of Rheumatology Immunology, The Second Xiangya Hospital of Central South University, Changsha.
J W
JW
Chen
Department of Rheumatology Immunology, The First Hospital of Changsha, Changsha, Hunan Province, China.
L X
LX
Chen
Department of Rheumatology Immunology, The Second Xiangya Hospital of Central South University, Changsha.
X
X
Xie
Department of Rheumatology Immunology, The Second Xiangya Hospital of Central South University, Changsha.
N
N
Mao
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000502:physiology*; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple; D005260:Female; D005347:Fibroblasts; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018501:Antirheumatic Agents; D008727:Methotrexate