Methotrexate suppresses the interleukin-6 induced generation of reactive oxygen species in the synoviocytes of rheumatoid arthritis

Citation
Jy. Sung et al., Methotrexate suppresses the interleukin-6 induced generation of reactive oxygen species in the synoviocytes of rheumatoid arthritis, IMMUNOPHARM, 47(1), 2000, pp. 35-44
Citations number
48
Categorie Soggetti
Immunology
Journal title
IMMUNOPHARMACOLOGY
ISSN journal
01623109 → ACNP
Volume
47
Issue
1
Year of publication
2000
Pages
35 - 44
Database
ISI
SICI code
0162-3109(200004)47:1<35:MSTIIG>2.0.ZU;2-Z
Abstract
Various cytokines and reactive oxygen species (ROS) play a fundamental role in the inflammatory and immunologic processes of rheumatoid arthritis (RA) . Methotrexate (MTX) is one of the disease-modifying anti-rheumatic drugs a nd its effect may be partly due to the modulation of immunologic or inflamm atory reactions by some cytokines. In the present study, we investigated th e effects of MTX on the gene expression and synthesis of interleukin-6 (IL- 6), and the proliferative activity and the production of ROS in the fibrobl ast-like synoviocytes (FLSs) obtained from the patient of RA. The expressio n or production of IL-6 was induced spontaneously, and augmented by the add ition of recombinant human IL-6 or recombinant human IL-1 beta and TNF-alph a in FLSs. These spontaneous and augmented IL-6 expressions or productions were suppressed by treatment with low-concentration of MTX (1 mu g/ml). Als o, IL-6 stimulated the proliferation of FLSs, and this IL-6 driven prolifer ation was inhibited with the treatment of MTX or N-acetylcysteine (NAC, 1 m M). Furthermore, ROS production in FLSs was increased significantly by IL-6 , and its effect was also abrogated in the presence of MTX or NAC. These re sults suggest that inflammatory reaction in the synovium of RA patients cou ld be augmented by the autocrine or other cytokine-induced production of IL -6 with subsequent generation of ROS in the synoviocytes, and the modulatio ns of IL-6 synthesis and ROS production may contribute to the therapeutic e ffects of MTX for RA. (C) 2000 Published by Elsevier Science B.V. All right s reserved.