Dual stimulation with bacterial and viral components increases the expression of hepcidin in human monocytes
Wiley Online Library
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Hepcidin belongs to the antimicrobial peptide (AMP) family and is the key regulator of iron metabolism. It modulates iron homeostasis by binding to, and degrading the iron exporter molecule, ferroportin, thus inhibiting cellular iron efflux. Many antimicrobial peptides have a dual function; some are able to act directly as an antimicrobial agent as well as having an immunoregulatory role in the host. Toll-like receptors (TLRs) bind to components of microorganisms, activate cellular signal transduction pathways and stimulate innate immune responses. The effect of TLR3 (poly I:C) and TLR9 (CpG) co-stimulation of THP-1-derived monocytes using purified TLR ligands showed that 24 h after exposure poly I:C and CpG ligands in combination, hepcidin expression was significantly increased (10-fold) when compared to the untreated control. This combination of TLR ligands mimics simultaneous bacterial and viral infections, thus suggesting a potential key role for hepcidin in combined infections. Additionally, using a chequerboard assay, we have shown that hepcidin has an antagonistic effect in combination with the antibiotics rifampicin and tetracycline against Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes, evidenced by a fractional inhibitory concentration index (FICI) > 4. This finding has important implications for future treatment regimens especially in an era of increasing antimicrobial resistance.
FEMS Microbiology Letters;
Ripley, D. A., Morris, R. H. and Maddocks, S. E. (2014), 'Dual stimulation with bacterial and viral components increases the expression of hepcidin in human monocytes', FEMS Microbiology Letters, 359, pp. 161–165.
Dynodwr Gwrthrych Digidol (DOI)http://dx.doi.org/10.1111/1574-6968.12553
This article was published in FEMS Microbiology Letters on 01 October 2014 available at http://dx.doi.org/10.1111/1574-6968.12553
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Exposure of Escherichia coli to human hepcidin results in differential expression of genes associated with iron homeostasis and oxidative stress Pascoe, Michael J.; Lueangsakultha, Jiraporn; Ripley, Delia; Morris, Keith; Maddocks, Sarah (Oxford University Press, 2018-04-06)Hepcidin belongs to the antimicrobial peptide family but has weak activity with regards to bacterial killing. The regulatory function of hepcidin in humans serves to maintain an iron-restricted environment that limits the ...
Hepcidin Gene Expression in THP-1 Monocyte, Macrophage & Dendritic Cells in Response to Synthetic Bacterial & Viral Ligands Mathias, Daniel (Cardiff Metropolitan University, 2017-06-01)Hepcidin was isolated at the beginning of the 21st century and is now regarded as the primary peptide responsible for iron homeostasis . Its interaction with FPN leads to its complete internalization and degradation, ...