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Cited by 30Immunotoxicology and immune responsesNeutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stress

Oxidative induction of pro-inflammatory cytokine formation by human monocyte-derived macrophages following exposure to manganese in vitro

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Mokgobu, Matlou I., Cholo, Moloko C., Anderson, Ronald, Steel, Helen C., Motheo, Maraki P., Hlatshwayo, Thembani N., Tintinger, Gregory R., Theron, Annette J.·2015·Journal of Immunotoxicology
DOI 10.3109/1547691x.2014.902877
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Abstract

Manganese (as Mn(2+)), a superoxide dismutase mimetic, catalyzes the formation of the relatively stable membrane-permeable reactive oxygen species (ROS) hydrogen peroxide (H2O2), a mediator of intracellular redox signaling in immune and inflammatory cells. The goal of this study was to investigate the potential for Mn(2+), via its pro-oxidative properties, to activate production of pro-inflammatory cytokines/chemokines IL-1β, IL-6, IL-8, IFNγ, TNFα, and G-CSF by human monocyte-derived macrophages in vitro. For these studies, the cells were isolated from peripheral blood mononuclear leukocytes and matured to generate a population of large CD14/CD16 co-expressing cells. The monocyte-derived macrophages were then exposed to bacterial lipopolysaccharide (LPS, 1 μg/ml) or MnCl2 (25-100 μM)-alone or in combination-for 24 h at 37 °C, after which cell-free supernatants were analyzed using a multiplex cytokine assay procedure. Exposure of the cells to LPS caused modest statistically insignificant increases in cytokine production; MnCl2 caused dose-related increases in production of all six cytokines (achieving statistical significance of p < 0.0171- < 0.0005 for IL-1β, IL-6, IL-8, IFNγ, and TNFα). In the case of LPS and MnCl2 combinations, the observed increases in production of IL-1β, IL-6, IL-8, IFNγ, and G-CSF were greater than those seen with cells exposed to the individual agents. The Mn(2+)-mediated induction of cytokine production was associated with increased production of H2O2 and completely attenuated by inclusion of the H2O2-scavenger dithiothreitol, and partially by inhibitors of NF-κB and p38MAP kinase. The findings from the studies here help to further characterize the pro-inflammatory mechanisms that may underpin clinical disorders associated with excess exposure to Mn(2+), particularly those disorders seen in the central nervous and respiratory systems.

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  • Excess manganese raises pro-inflammatory cytokine expression in macrophages.

    “manganese excess increases expression of pro-inflammatory cytokines from neuron-associated glial cells (Dodd and Filipov, 2011) and macrophages (Mokgobu et al., 2015)”

    From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Mokgobu et al., 2015

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Authors
Mokgobu, M. I., Cholo, M. C., Anderson, R., Steel, H. C., Motheo, M. P., Hlatshwayo, T. N., Tintinger, G. R., & Theron, A. J.
Affiliations
  • Tshwane University of Technology (ZA)
  • University of Pretoria (ZA)
  • National Health Laboratory Service (ZA)
Corresponding author
Theron, Annette J.
ORCID
Venue
Journal of Immunotoxicology
Publisher
Informa UK Limited
Published
2014-05-07
Volume
12
Issue
1
Pages
98-103
ISSN
  • 1547-6901 (ISSN-L)
  • 1547-691X
DOI
10.3109/1547691x.2014.902877
OpenAlex
W2060647682
Cited by
30
References
31
Citations by year
2026: 1 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 1
FWCI
1.37
Type
journal article
Language
en
Open access
Locations
  • Journal of Immunotoxicology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
manganese, monocyte-derived macrophages, inflammatory cytokines, reactive oxygen species, hydrogen peroxide, lipopolysaccharide, NF-κB, p38 MAPK, dithiothreitol, superoxide dismutase mimetic, neurotoxicity, respiratory toxicity, IL-1β, interleukin-6, interleukin-8, interferon-gamma, TNF-α, granulocyte colony-stimulating factor
MeSH terms
Adult, Cells, Cultured, Chlorides, Dithiothreitol, Female, Humans, Hydrogen Peroxide, Imidazoles, Lipopolysaccharides, Macrophages, Male, Middle Aged, Oxidation-Reduction, Pyridines, Respiratory Tract Diseases, Cytokines, Occupational Exposure, NF-kappa B, Manganese Compounds, Inflammation Mediators, Manganese Poisoning, MAP Kinase Signaling System, Young Adult

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