Increase of Cyclooxygenase-2 Expression by Interleukin 15 in Rheumatoid Synoviocytes

So Youn Min, Sue Yun Hwang, Young Ok Jung, Jinyoung Jeong, Sung Hwan Park, Chul Soo Cho, Ho Youn Kim, Wan Uk Kim

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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-1β tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) in the culture supernatants. Results. EL-15 dose-dependently increased COX-2 mRNA and protein expression in FLS, but not the COX-1 mRNA level. Both IL-1β and TNF-α upregulated COX-2 mRNA comparably to IL-15, but neither IL-2 nor interferon-γ had any effect on the COX-2 mRNA level. Treatment with anti-IL-1β or anti-TNF-α 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-κB (NF-κB) 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 PGE 2-dependent manner. The activation of NF-κB 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-1β and TNF-α production.

Original languageEnglish (US)
Pages (from-to)875-883
Number of pages9
JournalJournal of Rheumatology
Volume31
Issue number5
StatePublished - May 1 2004

Keywords

  • Cyclooxygenase-2
  • Interleukin 15
  • Nuclear factor-κB
  • Synoviocytes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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  • Cite this

    Min, S. Y., Hwang, S. Y., Jung, Y. O., Jeong, J., Park, S. H., Cho, C. S., Kim, H. Y., & Kim, W. U. (2004). Increase of Cyclooxygenase-2 Expression by Interleukin 15 in Rheumatoid Synoviocytes. Journal of Rheumatology, 31(5), 875-883.