Expression of the thioredoxin-thioredoxin reductase system in the inflamedjoints of patients with rheumatoid arthritis

Objective, To examine the expression of the thioredoxin (TRX)-thioredoxin r eductase (TR) system in patients with rheumatoid arthritis (RA) and patient s with other rheumatic diseases, Methods. Levels of TRX in plasma and synovial fluid (SF) were measured usin g enzyme-linked immunosorbent assay, Cellular distribution of TRX was deter mined by flow cytometry and histochemistry. Cellular expression of TR was s tudied by in situ messenger RNA (mRNA) hybridization. The effect of oxidati ve stress and tumor necrosis factor alpha (TNF alpha) on TRX expression by cultured rheumatoid fibroblast-like synoviocytes was studied. Results, Significantly increased TRX levels were found in the SF from 22 pa tients with RA, when compared with plasma levels in the same patients (P < 0.001) and compared with SF TRX levels in 15 patients with osteoarthritis ( P < 0.001), 13 patients with gout (P < 0.05), and 9 patients with reactive arthritis (P < 0.0001), The presence of TRX could be demonstrated within th e SE-derived mononuclear cells and synovial tissue (ST) of RA patients. Con cordantly, expression of TR mRNA was observed in the ST of these patients, Stimulation of synovial fibroblast-like synoviocytes with either H2O2 or TN F alpha induced an increase in the production of TRX. Conclusion. The data demonstrate significantly increased concentrations of TRX in the SF and ST of RA patients when compared with the levels in patien ts with other joint diseases. Evidence is presented that the local environm ent in the rheumatic joint contributes to increased TRX production, Based o n its growth-promoting and cytokine-like properties, it is proposed that in creased expression of TRX contributes to the disease activity in RA.