{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:11:14Z","timestamp":1789960274003,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2002,5,8]],"date-time":"2002-05-08T00:00:00Z","timestamp":1020816000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the antiangiogenic effect of cyclosporin A (CSA) in rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the effect of CSA on the production of vascular endothelial growth factor (VEGF) by rheumatoid synovial fibroblasts. Fibroblast\u2010like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of CSA. The production of VEGF by FLS was measured in culture supernatants by enzyme\u2010linked immunosorbent assay. The VEGF messenger RNA (mRNA) expression and activator protein 1 (AP\u20101) binding activity for VEGF transcription were determined by polymerase chain reaction and electrophoretic mobility shift assay, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CSA dose\u2010dependently inhibited both constitutive and transforming growth factor \u03b2\u2010induced VEGF production at the protein and mRNA levels. The suppressive action of CSA on VEGF synthesis was calcineurin dependent, as evidenced by a comparable inhibition by FK\u2010506. Agonists of cAMP, 3\u2010isobutyl\u20101\u2010methylxanthine and <jats:italic>N<\/jats:italic>\u20102\u2010<jats:italic>O<\/jats:italic>\u2010dibutyryl\u2010cAMP, mimicked the effect of CSA on VEGF production, while a cAMP antagonist, 2\u2032,3\u2032\u2010dideoxyadenosine, abrogated the effect of CSA. A gel mobility shift assay showed that the inhibitory effect of CSA was associated with decreased AP\u20101 binding activity to the VEGF promoter, in a cAMP\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CSA may exert an antiangiogenic effect by inhibiting AP\u20101\u2010mediated VEGF expression in rheumatoid synovial fibroblasts.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10215","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T12:20:06Z","timestamp":1033906806000},"page":"1202-1209","source":"Crossref","is-referenced-by-count":58,"title":["Cyclosporine inhibition of vascular endothelial growth factor production in rheumatoid synovial 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