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

Objective-To examine the effect of iron on the prostaglandin (PG) E-2 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 PGE(2) in the culture medium was measured by an enzyme linked immunosorbent assay. Results-The production of PGE(2) 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 PGE(2) by the synovial fibroblasts, both with and without stimulation by IL1 beta. Fe-citrate inhibited the spontaneous PGE, 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 mu g/ml), an iron chelator. Conclusion-Iron down regulates the PGE(2) production by synovial fibroblasts in vitro.