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

Abstract

Objective-To examine the eVect 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 (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 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 . Fe-citrate inhibited the spontaneous PGE 2 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 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 PGE 2 production by synovial fibroblasts in vitro.

Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E2 synthesis: In vitro and in vivo studies

“…Interestingly, these authors found a comparable increase of PGE 2 by desferrioxamine in absence of ferric citrate. This suppressive effect of soluble ferric citrate on PGE 2 in fibroblasts [ 34 ] contrasts our findings that more soluble iron enhances PGE 2 synthesis in AM. Reasons for this discrepancy between the two studies may be due to the amount of soluble iron that existed in extracellular milieu in the Hisakawa study.…”

“…Hisakawa et al [34] observed a depletion of PGE 2 in human synovial fibroblasts by soluble ferric citrate, which could be reversed by the presence of desferrioxamine. Interestingly, these authors found a comparable increase of PGE 2 by desferrioxamine in absence of ferric citrate.…”

“…Externally added vanadium and zinc have been shown to inhibit phosphatases and induce kinase-specific signaling in cells and subsequent inflammation [ 33 ]. Hisakawa et al [ 34 ] observed a depletion of PGE 2 in human synovial fibroblasts by soluble ferric citrate, which could be reversed by the presence of desferrioxamine. Interestingly, these authors found a comparable increase of PGE 2 by desferrioxamine in absence of ferric citrate.…”

Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation

“…Therefore, our work highlighted a marked decrease in mechanosensitivity of osteocytes under iron overload. Moreover, generation of oxidative stress has been implicated in inhibitory effects of iron in the production of prostaglandin E 2 and nitric oxide 33 , 34 . Therefore, it is tempting to speculate that accumulation of intracellular iron induces the loss of mechanosensitivity in osteocytes by inhibiting the synthesis of these two molecules.…”

The Effect of High Dosage of Iron Supplementation (Fe) Against Histopathology of Gastric Mucosa in Pregnant Strain Wistar White Rats (Rattus norvegicus)

“…Iron can inhibit the production of prostaglandins. Inhibition of prostaglandin synthesis in the stomach will increase acid secretion, and cut off the defense of the gastric mucosa (Hisakawa et al, 1998). These conditions can cause irritation to the stomach and result in damage to the mucosa, parietal cells, and endothelial cells (Shibata-Nozaki et al, 2011).…”