Down regulation by iron of prostaglandin E2production by human synovial fibroblasts

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.

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