%0 Journal Article %A Lisa K Stamp %A Leslie G Cleland %A Michael J James %T Upregulation of synoviocyte COX-2 through interactions with T lymphocytes: role of interleukin 17 and tumor necrosis factor-alpha. %D 2004 %J The Journal of Rheumatology %P 1246-1254 %V 31 %N 7 %X OBJECTIVE: T lymphocytes infiltrating rheumatoid synovium may alter the function of resident synoviocytes. We investigated the influence on synoviocyte cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production exerted by soluble factors released by T cells, with particular reference to interleukin 17 (IL-17). METHODS: Human peripheral blood T cells were stimulated with antibodies directed against CD3 and CD28. Harvested T cell supernatants were applied to cultured human fibroblast-like synoviocytes in culture. The effects of IL-17 alone and in combination with tumor necrosis factor-a (TNF-a) were examined using recombinant cytokines and neutralizing antibodies. Synoviocyte COX-2 expression and PGE2 production were examined. RESULTS: Supernatants from stimulated T cells upregulated COX-2 expression and increased PGE2 production by synoviocytes. The T cell supernatants were found to contain IL-17 and TNF-a. Recombinant IL-17 upregulated synoviocyte COX-2 expression and enhanced TNF-a stimulated synoviocyte COX-2 expression. The upregulation of synoviocyte COX-2 expression by supernatants from stimulated T cells was partially inhibited by addition of neutralizing antibodies against IL-17 or TNF-a or by treatment of T cells with cyclosporin A prior to stimulation. CONCLUSION: Activated T cells are capable of paracrine upregulation of synoviocyte COX-2 expression and PGE2 production through release of soluble mediators. T cell derived IL-17, especially in combination with TNF-a, may contribute to ongoing inflammation through its effects on COX-2 expression and PGE2 production. These data provide additional evidence for the contribution of T cells in rheumatoid inflammation and highlight the potential of IL-17 as a therapeutic target. %U https://www.jrheum.org/content/jrheum/31/7/1246.full.pdf