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In vivo role(s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammation

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Abstract

The maintenance of iron homeostasis is critical as both iron deficiency and iron excess are deleterious. In mammals, iron homeostasis is regulated systemically by the iron-hormone hepcidin, an acute-phase protein secreted by the liver which inhibits iron absorption and recycling. Cellularly, the interaction of iron regulatory proteins (IRP) 1 and 2 with iron-responsive elements controls the expression of target mRNAs encoding proteins of iron acquisition, storage, utilization, and export. These processes critically affect iron levels, which in turn impact on numerous aspects of inflammation. To explore the role of IRP1 and IRP2 in inflammation, IRP-deficient mice, i.e., mice with total and constitutive deficiency of either IRP, were subjected to acute aseptic local inflammation. Turpentine oil injection increases the expression of acute phase proteins in the liver and interleukin 6 levels in the serum of control mice. Both IRP-deficient mouse models mount the same responses, indicating that the treatment was efficient in all animals and that the acute phase response does not require expression of both IRPs. As expected, turpentine oil treatment enhances hepcidin mRNA expression in the liver of wild-type mice, associated with decreased serum iron levels. Importantly, Irp1 −/− and Irp2 −/− animals, respectively, display quantitatively similar hepcidin mRNA induction and the appropriate reduction of the serum iron values. Our data indicate that the response of Irp1 −/− and Irp2 −/− mice to acute local inflammation is largely preserved.

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Acknowledgments

We thank Dunja Ferring-Appel for technical help and the staff of the EMBL’s Laboratory of Animal Resources for providing dedicated animal care. This work was supported by an EMBO long-term fellowship to L.V. (ALTF 957-2005) and by an EEC FP6 grant (LSHM-CT-2006-037296 Euroiron1) to M.W.H.

Conflict of interest

The authors declare that they have no competing financial interests.

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Authors and Affiliations

  1. European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117, Heidelberg, Germany

    Lydie Viatte, Matthias W. Hentze & Bruno Galy

  2. Abteilung Zelluläre und Molekulare Pathologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Hermann-Josef Gröne

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  1. Lydie Viatte
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  2. Hermann-Josef Gröne
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Correspondence to Matthias W. Hentze.

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Viatte, L., Gröne, HJ., Hentze, M.W. et al. In vivo role(s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammation. J Mol Med 87, 913–921 (2009). https://doi.org/10.1007/s00109-009-0494-8

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  • DOI: https://doi.org/10.1007/s00109-009-0494-8

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