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Down regulation by iron of prostaglandin E2 production by human synovial fibroblasts
N Hisakawa1, K Nishiya, K Tahara
1Second Department of Internal Medicine, Kochi Medical School, Nankoku City, Japan.
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) 1 beta (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 IL1 beta 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 IL1 beta. 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 IL1 beta stimulation. The down regulation by iron was reversed by the co-addition of desferrioxamine (100 micrograms/ml), an iron chelator.
Conclusion:
Iron down regulates the PGE2 production by synovial fibroblasts in vitro.