Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux

Copper is known to play a role in iron recycling from macrophages. To examine whether cellular copper status affects expression of the iron exporter ferroportin-1 (FPN1), J774 macrophage cells were exposed to 10-100 microM CuSO(4) for up to 20 h. Copper treatment significantly increased FPN1 mRNA in a dose- and time-dependent manner. After 20 h, 100 microM CuSO(4) up-regulated FPN1 transcript levels approximately 13-fold compared to untreated controls. Induction was detected 8 h after copper treatment was initiated and markedly increased thereafter. A corresponding increase in FPN1 protein levels was observed upon copper treatment. Induction of J774 cell FPN1 expression by copper was also associated with a dose-dependent increase in (59)Fe release after erythrophagocytosis of labeled red blood cells. Thus, a previously uncharacterized role for copper in the regulation of macrophage iron recycling is suggested by the induction of FPN1 gene expression and iron efflux by this metal.