Relationship between TNF-α and iron metabolism in differentiating human monocytic THP-1 cells

A. Scaccabarozzi, P. Arosio, G. Weiss, L. Valenti, P. Dongiovanni, A. L. Francanzani, M. Mattioli, S. Levi, G. Fiorelli, S. Fargion

Research output: Contribution to journalArticlepeer-review


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 α (TNF-α) by interferon γ (IFN-γ) 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-α mRNA and TNF-α secretion to levels even higher than those induced by IFN-γ alone. The iron chelator desferrioxamine showed the opposite effect and reduced TNF-α release. In contrast, preincubation of the cells with iron before PMA induction resulted in a decrease of the TNF-α secretion induced by IFN-γ, whereas the opposite was true after preincubation with desferrioxamine. The data support a coordinate interaction between iron and TNF-α in monocyte macrophages, with an iron-mediated upregulation of TNF-α 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.

Original languageEnglish
Pages (from-to)978-984
Number of pages7
JournalBritish Journal of Haematology
Issue number4
Publication statusPublished - 2000


  • H ferritin
  • Inflammation
  • Iron
  • TNF-α
  • Transferrin receptor

ASJC Scopus subject areas

  • Hematology


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