Down regulation by iron of prostaglandin E-2 production by human synovial fibroblasts

Objective-To examine the effect of iron on the prostaglandin (PG) E-2 produ ction by human synovial fibroblasts in vitro. Methods-Human synovial fibroblasts were isolated from synovial tissue of rh eumatoid arthritis (RA) and osteoarthritis (OA) patients and cultured in me dium. Synovial fibroblasts were stimulated by human recombinant interleukin (IL) 1 beta (0.1-10 ng/ml) with or without ferric citrate (Fe-citrate, 0.0 1-1 mM). The amount of PGE(2) in the culture medium was measured by an enzy me 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 n ot sodium citrate (Na-citrate) down regulated the production of PGE(2) by t he synovial fibroblasts, both with and without stimulation by IL1 beta. Fe- citrate inhibited the spontaneous PGE, production by the cells in a dose de pendent 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 i ron was reversed by the co-addition of desferrioxamine (100 mu g/ml), an ir on chelator. Conclusion-Iron down regulates the PGE(2) production by synovial fibroblast s in vitro.