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Bacterial Cell Wall Constituents Induce Hepcidin Expression in Macrophages Through MyD88 Signaling

Inflammation volume 35, pages 1500–1506 (2012)Cite this article

Abstract

Hepcidin is a key regulator of iron recycling by macrophages that is synthesized mainly by hepatocytes but also by macrophages. However, very little is known about the molecular regulation of hepcidin in macrophages. In the present study, we investigated hepcidin regulation in the RAW264.7 macrophage cell line and in murine peritoneal macrophages stimulated with different Toll-like receptor (TLR) ligands. We found that TLR-2 and TLR-4 ligands activated hepcidin expression in RAW264.7 cells and in wild-type murine peritoneal macrophages, but not in murine peritoneal macrophages isolated from TLR2−/−, TLR-4-deficient or MyD88−/− mice. IL-6 production by RAW264.7 cells stimulated with lipopolysaccharide (LPS, TLR4 ligand) was enhanced by high amounts of iron present in the culture medium. We conclude that hepcidin expression in macrophages is regulated mainly through TLR2 and TLR4 receptors via the MyD88-dependent signaling pathway and that autocrine regulation of iron accumulation in macrophages by hepcidin may affect the levels of proinflammatory cytokine production.

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Acknowledgments

We acknowledge the help of Dr. Peter P. Liu from the Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Canada with the MyD88−/− mouse. This work was supported by a grant from the Canadian Institutes of Health Research (CIHR, grant no. MOP44045). AL is the recipient of a Ph.D. scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). MMS is the recipient of a research scholarship (Senior) from the FRSQ (Fonds de la recherche en santé du Québec).

Contributions

AL designed and performed experiments, collected, and analyzed the data, and wrote the manuscript; and MMS designed the experiments, analyzed the data, and critically reviewed the manuscript.

Conflict of interest

The authors declare no competing financial interests.

Author information

Affiliations

  1. Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Hôpital Notre-Dame, Pav. De Sève Y5625, 1560 rue Sherbrooke est, Montréal, Québec, H2L 4M1, Canada

    Antonio Layoun

  2. Institut du cancer de Montréal, Montreal, Quebec, Canada

    Antonio Layoun & Manuela M. Santos

  3. Département de Médecine, Université de Montréal, Montréal, Québec, Canada

    Manuela M. Santos

  4. Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Pav. De Sève Y5625, 1560 rue Sherbrooke est, Montréal, Québec, H2L 4M1, Canada

    Manuela M. Santos

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  1. Antonio Layoun
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Correspondence to Manuela M. Santos.

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Layoun, A., Santos, M.M. Bacterial Cell Wall Constituents Induce Hepcidin Expression in Macrophages Through MyD88 Signaling. Inflammation 35, 1500–1506 (2012). https://doi.org/10.1007/s10753-012-9463-4

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  • DOI: https://doi.org/10.1007/s10753-012-9463-4

KEY WORDS

  • hepcidin
  • iron
  • macrophages
  • inflammation
  • TLR
  • MyD88
  • hypoferremia