Relationship between TNF-alpha and iron metabolism in differentiating human monocytic THP-1 cells.
The human monocytic cell line THP-1 differentiates along the macrophage line after phorbol-12-myristate-13-acetate (PMA) supplementation and can be stimulated to secrete tumour necrosis factor alpha (TNF-alpha) by interferon gamma (IFN-gamma) addition. We found that, in the early stage of differentiation (1-48 h), PMA induction elicited an upregulation of intracellular H ferritin and H ferritin binding sites and a downregulation of transferrin receptor. In addition, we found that iron administration to PMA-differentiating cells induced the expression of TNF-alpha mRNA and TNF-alpha secretion to levels even higher than those induced by IFN-gamma alone. The iron chelator desferrioxamine showed the opposite effect and reduced TNF-alpha release. In contrast, preincubation of the cells with iron before PMA induction resulted in a decrease of the TNF-alpha secretion induced by IFN-gamma, whereas the opposite was true after preincubation with desferrioxamine. The data support a co-ordinate interaction between iron and TNF-alpha in monocyte macrophages, with an iron-mediated upregulation of TNF-alpha in the early phase of differentiation and an iron-mediated inhibition at later stages. This complex relationship has to be considered in evaluating the effects of iron on inflammation.
Scaccabarozzi
A
A
Department of Internal Medicine, Maggiore Hospital, IRCCS, University of Milan, Italy.
Arosio
P
P
Weiss
G
G
Valenti
L
L
Dongiovanni
P
P
Fracanzani
A L
AL
Mattioli
M
M
Levi
S
S
Fiorelli
G
G
Fargion
S
S
D001665:Binding Sites; D015152:Blotting, Northern; D002454:Cell Differentiation; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002614:Chelating Agents; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; D013755:Tetradecanoylphorbol Acetate