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

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

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The human monocytic cell line THF-1 differentiates along the macrophage line after phorbol-12-myristate-13-acetate supplementation and can be stimulated to secrete tumor necrosis factor a by Interferon g addition. We found that in the early stage of differentiation (1-48 hours) phorbol-myristate-acetate induction elicited an upregulation of intracellular H ferritin and H ferritin binding sites, and a down-regulation of transferrin receptor. In addition, we found that iron administration to phorbol-myristate-acetate differentiating cells induced the expression of tumor necrosis factor a mRNA and tumour necrosis factor a secretion to levels even higher than those induced by Interferon g alone. The iron chelator desferrioxamine showed the opposite effect and reduced tumour necrosis factor a release. In contrast, pre-incubation of the cells with iron, before phorbol-myristate-acetate induction, resulted in a decrease of the tumour necrosis factor a secretion induced by Interferon g, while the opposite was true for a pre-incubation with desferrioxamine. The data support a coordinate interaction between iron and TNFa in monocyte-macrophages, with an ironmediated upregulation of tumour necrosis factor a 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
Issue number11 PART II
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hematology


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