Down regulation by iron of prostaglandin E₂ production by human synovial fibroblasts

Abstract

OBJECTIVE—To examine the effect of iron on the prostaglandin (PG) E₂ production by human synovial fibroblasts in vitro.
METHODS—Human synovial fibroblasts were isolated from synovial tissue of rheumatoid arthritis (RA) and osteoarthritis (OA) patients and cultured in medium. Synovial fibroblasts were stimulated by human recombinant interleukin (IL) 1β (0.1-10 ng/ml) with or without ferric citrate (Fe-citrate, 0.01-1 mM). The amount of PGE₂ in the culture medium was measured by an enzyme linked immunosorbent assay.
RESULTS—The production of PGE₂ by the synovial fibroblasts was increased by stimulation with IL1β at all concentrations tested. Fe-citrate but not sodium citrate (Na-citrate) down regulated the production of PGE₂ by the synovial fibroblasts, both with and without stimulation by IL1β. Fe-citrate inhibited the spontaneous PGE₂ production by the cells in a dose dependent manner, and a maximum inhibition by Fe-citrate was observed at the concentration of 0.1 mM with IL1β stimulation. The down regulation by iron was reversed by the co-addition of desferrioxamine (100 µg/ml), an iron chelator.
CONCLUSION—Iron down regulates the PGE₂ production by synovial fibroblasts in vitro.

 Keywords: rheumatoid arthritis; joint inflammation; cyclooxygenase; cytokine; inflammatory mediators

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Figure 1  .

Effects of ferric citrate and sodium citrate on the PGE₂ production by human synovial cells stimulated without or with different concentrations of IL1β. Data are the mean (SEM) of six separate experiments using cells from different patients. * p < 0.05, ** p < 0.01 compared with medium alone.

Figure 2  .

(A) Effects of three different concentrations of ferric citrate on the spontaneous PGE₂ production by human synovial cells in a time course study. Data are the mean (SEM) of five experiments. * p < 0.05 compared with medium alone. (B) Effects of three different concentrations of ferric citrate on the PGE₂ production by human synovial cells with stimulation by 1 ng/ml IL1β in a time course study. Data are the mean (SEM) of five experiments. * p < 0.05, ** p < 0.01 compared with medium alone.