%0 Journal Article %A So-Youn Min %A Sue-Yun Hwang %A Young-Ok Jung %A Jinyoung Jeong %A Sung-Hwan Park %A Chul-Soo Cho %A Ho-Youn Kim %A Wan-Uk Kim %T Increase of cyclooxygenase-2 expression by interleukin 15 in rheumatoid synoviocytes. %D 2004 %J The Journal of Rheumatology %P 875-883 %V 31 %N 5 %X OBJECTIVE: To determine the effect of interleukin 15 (IL-15) on cyclooxygenase-2 (COX-2) expression in rheumatoid synoviocytes. METHODS: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of patients with rheumatoid arthritis (RA) and cultured in the presence of IL-15. Levels of COX-2 mRNA and protein expression were determined by reverse transcription-polymerase chain reaction and Western blot, respectively. ELISA was used to measure concentrations of IL-1beta, tumor necrosis factor-a (TNF-a), and prostaglandin E2 (PGE2) in the culture supernatants. RESULTS: IL-15 dose-dependently increased COX-2 mRNA and protein expression in FLS, but not the COX-1 mRNA level. Both IL-1beta and TNF-a upregulated COX-2 mRNA comparably to IL-15, but neither IL-2 nor interferon-g had any effect on the COX-2 mRNA level. Treatment with anti-IL-1beta or anti-TNF-a antibodies partially reduced the IL-15-stimulated COX-2 mRNA expression, suggesting that these cytokines may take part in modulating COX-2 by IL-15. Dexamethasone and pyrolidine dithiocarbamate, but not curcumin, completely blocked the IL-15-induced upregulation of COX-2 mRNA. A gel mobility shift assay revealed that nuclear factor-kB (NF-kB) was one of the major signal molecules to mediate IL-15-induced COX-2 upregulation. The increase of COX-2 by IL-15 is PGE2-dependent because exogenous PGE2 reversed the suppressive effect of NS-398, a selective COX-2 inhibitor, on COX-2 mRNA and protein expression. CONCLUSION: This study confirms the effect of IL-15 on upregulation of COX-2 in a PGE2-dependent manner. The activation of NF-kB bound to the COX-2 promoter appears to be a downstream target of IL-15 stimulation in FLS, exerted either directly or through the increase in IL-1beta and TNF-a production. %U https://www.jrheum.org/content/jrheum/31/5/875.full.pdf