ArticleClinical and experimental immunology2004
Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1beta stimulated rheumatoid synovial fibroblasts.
Article in Clinical and experimental immunology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 27 citations in OpenAlex.
- Preliminary evaluation in rheumatoid arthritis activity in patients treated with TNF-alpha blocker plus methotrexate versus methotrexate or leflunomide alone.Rheumatology international · 2007Trial
- The Role of Pharmacogenetics in the Effectiveness of Rheumatoid Arthritis Treatment with Leflunomide.Genes · 2026Review
- De novo identification of toxicants that cause irreparable damage to parasitic nematode intestinal cells.PLoS neglected tropical diseases · 2020Article
- Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells.Experimental biology and medicine (Maywood, N.J.) · 2015Article
- Role of oral teriflunomide in the management of multiple sclerosis.Neuropsychiatric disease and treatment · 2013Article
- Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions.Journal of inflammation (London, England) · 2012Article
- Different expression levels of TNF receptors on the rheumatoid synovial macrophages derived from surgery and a synovectomy as detected by a new flow cytometric analysis.Cytotechnology · 2009Article
- Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts.Arthritis research & therapy · 2007Article
- Serum Amyloid A in Inflammatory Rheumatic Diseases: A Compendious Review of a Renowned Biomarker.Frontiers in immunologyReview
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.
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