PT  - JOURNAL ARTICLE
AU  - Lisa K.  Stamp
AU  - Jody Hazlett
AU  - John Highton
AU  - Paul A.  Hessian
TI  - Expression of Methotrexate Transporters and Metabolizing Enzymes in Rheumatoid Synovial Tissue
AID  - 10.3899/jrheum.130066
DP  - 2013 Jul 15
TA  - The Journal of Rheumatology
PG  - jrheum.130066
4099  - http://www.jrheum.org/content/early/2013/07/11/jrheum.130066.short
4100  - http://www.jrheum.org/content/early/2013/07/11/jrheum.130066.full
AB  - Objective To determine whether methotrexate (MTX) affects the expression of genes involved in the transport [SLC19A1 (RFC1), ABCB1 (MDR1), ABCC1 (multidrug resistance proteins 1), ABCG2 (BCRP)], metabolism [γ-glutamyl hydrolase (GGH), folylpolyglutamate synthetase (FPGS)], and mechanism of action of MTX [thymidylate synthase, MTR, MTRR] in rheumatoid synovium. Methods Synovial tissue samples were obtained from 20 patients with rheumatoid arthritis (RA). Gene expression was undertaken using quantitative real-time PCR. Results All the genes examined were expressed in all samples. Expression of SLC19A1, GGH, FPGS, ABCC1, and MTRR was significantly higher in patients receiving MTX compared to those not receiving MTX (p < 0.05). The ratio of FPGS:GGH gene expression was 2.7 ± 0.51 ng/ml GAPDH (range 0.67–9.58). Conclusion Genes involved in the transport, metabolism, and mechanism of action of MTX are expressed in rheumatoid joint synovium. These data provide evidence that MTX has the potential to be polyglutamated within the joint. The higher expression of FPGS compared to GGH in synovial tissue might favor production of long-chain MTX polyglutamates. Thus MTX has the potential to exert its therapeutic effects at the primary site of the inflammatory process in RA.