Hepcidin generated by hepatoma cells inhibits iron export from co-cultured THP1 monocytes

Expression of the subgenomic hepatitis C virus replicon alters iron homeostasis in Huh7 cells

“…Even though this is a strong indication of an iron-deficient phenotype, as human IRE/IRP1 and IRE/IRP2 complexes co-migrate in EMSA [49], and IRP1 is also induced by H 2 O 2 [50], an increase in total IRE-binding activity could also be indicative of oxidative stress. By assessing IRP2 levels, which serve as a sensitive marker of cellular iron status [39,51], we found that the expression of IRP2 was significantly (p < 0.01) upregulated in replicon cells, to the same degree as in DFO-treated parent cells (Fig. 3b).…”

“…Following three times washes with non-radioactive icecold media, half of the cells were harvested and counted for radioactivity on a c-counter, to determine 59 Fe uptake. The remaining cells were further incubated in serum-free media containing 100 lM high molecular weight DFO, and the radioactivity of culture supernatants was measured at specified time intervals on a c-counter, to monitor 59 Fe release [39].…”

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

“…36 We investigated putative interactions between macrophages, HCV and iron by utilizing an indirect co-culture system of THP-1 macrophages with Huh7.5 hepatoma cells. Such in vitro systems have been extensively used to unravel cellular communication through soluble factors 37 , including hepcidin, 22,38 as well as other aspects of liver/macrophage biology. 39 Evidently, hepatoma hepcidin expression was increased faster in the co-culture than the monoculture system.…”

Hepcidin targets ferroportin for degradation in hepatocytes

“…Hepcidin, the iron-regulatory hormone secreted by the hepatocyte, is indeed able to bind to ferroportin inducing its internalization, ubiquitination and degradation, as shown in transfected cell lines. 4,5 While the effect of hepcidin on endogenous ferroportin was clearly demonstrated in macrophagic cell types, [6][7][8][9][10] exposure of intestinal epithelial cells to hepcidin was reported to have no effect on ferroportin levels 9 and hepcidininduced duodenal ferroportin regulation was only shown indirectly in mouse models of iron disorders. [11][12][13][14][15][16] Apart from enterocytes and macrophages, not much is known concerning the presence of the iron exporter ferroportin in hepatocytes.…”