Modulation of iron metabolism in monocyte cell line U937 by inflammatory cytokines: changes in transferrin uptake, iron handling and ferritin mRNA.

Fahmy, M; Young, S P

doi:10.1042/bj2960175

Cited by 150Iron Metabolism and DisordersNeurological diseases and metabolismTrace Elements in Health

Modulation of iron metabolism in monocyte cell line U937 by inflammatory cytokines: changes in transferrin uptake, iron handling and ferritin mRNA.

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Fahmy, M, Young, S P·1993·Biochemical Journal

DOI 10.1042/bj2960175PMC PMC1137671

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Abstract

We have investigated the effects of the pro-inflammatory cytokines interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) on the iron metabolism of the human monocytic cell line U937. Cells were treated with each cytokine for up to 24 h, and then iron uptake from diferric transferrin was determined. The intracellular distribution of this iron, the expression of the transferrin receptor and levels of mRNA for the two ferritin subunits were also studied. IL-1 beta, TNF alpha and IFN gamma all decreased transferrin-iron uptake into cells, and all three cytokines had effects on the proportion of iron associated with ferritin. With TNF alpha there was a marked enhancement of the fraction incorporated into ferritin. Transferrin-receptor expression was diminished by TNF alpha and IL-1 beta, but not IFN gamma, suggesting different effector mechanisms. Both TNF alpha and IFN gamma increased the amount of cellular mRNA for ferritin H-chain, but not the L-chain; IL-1 beta affected mRNA for neither ferritin. These data demonstrate that cytokines, which can be present at high concentrations in inflammation, have the capacity to affect macrophage iron uptake, transferrin receptor expression, intracellular iron handling and the relative abundance of ferritin-subunit mRNA, and may therefore be important mediators in the observed perturbations of iron metabolism in inflammatory diseases.

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TNF-α, IL-1, IL-6, and IFN-γ affect macrophage iron homeostasis by increasing the uptake of transferrin and non-transferrin bound iron via modulating the expression of transferrin receptor-1 and divalent metal transporter-1.
“Second, TNF-α, IL-1, IL-6, and interferon-gamma (IFN-γ) affect macrophage iron homeostasis by different avenues. They increase the uptake of transferrin and non-transferrin bound iron by modulating the expression of transferrin receptor-1 and divalent metal transporter-1, respectively (Byrd and Horwitz, 1993; Fahmy and Young, 1993; Mulero and Brock, 1999; Ludwiczek et al., 2003).”
From Iron at the interface of immunity and infection (2014) · cites this paper as Fahmy and Young, 1993

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Authors: Fahmy, M., & Young, S. P.
Affiliations: University of Birmingham (GB)
ORCID: Young, S P
Venue: Biochemical Journal
Publisher: Portland Press Ltd.
Published: 1993-11-15
Volume: 296
Issue: 1
Pages: 175-181
ISSN: 0264-6021 (ISSN-L)
1470-8728
DOI: 10.1042/bj2960175
PMC: PMC1137671
OpenAlex: W2258966438
Cited by: 150
References: 53
Citations by year: 2026: 1 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 1
FWCI: 2.27
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: iron metabolism, inflammatory cytokines, IL-1β, TNF-α, interferon-gamma, U937 cells, monocytes, transferrin uptake, transferrin receptor, ferritin mRNA, macrophages, inflammation
MeSH terms: Biological Transport, Cell Line, Ferritins, Humans, Inflammation, Interferon-gamma, Interleukin-1, Iron, Kinetics, Monocytes, RNA, Messenger, Time Factors, Transferrin, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Gene Expression, Cytokines

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Modulation of iron metabolism in monocyte cell line U937 by inflammatory cytokines: changes in transferrin uptake, iron handling and ferritin mRNA.

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