Iron responses in hepatic, intestinal and macrophage/monocyte cell lines under different culture conditions.
Iron homeostasis is mainly controlled by the liver-produced hepcidin peptide, which induces the degradation of the ferroportin iron exporter and thus regulates serum iron level. Hepcidin transcription is clearly up-regulated by the pro-inflammatory cytokine IL-6 and down-regulated, in the case of iron depletion, at least via HIF transcription factors. In addition, in vivo iron overload up-regulates hepcidin, but this cannot be reproduced in cell culture or isolated hepatocytes. Here, we investigated the steady state mRNA levels of a series of genes involved in iron metabolism in hepatic HepG2, intestinal Caco-2, and monocyte/macrophage THP-1 cell lines under different iron and culture conditions. Our results showed that iron-saturated transferrin up-regulated hepcidin mRNA synthesis from HepG2 via cross-talk with macrophages or enterocyte cytokine-producing cells, whereas non-transferrin-bound iron down-regulated hepcidin, likely due to missing TfR-iron-transferrin uptake.
Jacolot
Sandrine
S
INSERM U613 Génétique moléculaire et génétique épidémiologique, 46 rue Félix Le Dantec, F-29200 Brest, France.
Férec
Claude
C
Mura
Catherine
C
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D020895:Enterocytes / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D017077:Culture Media, Conditioned; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D012333:RNA, Messenger; D014168:Transferrin; D007501:Iron