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Licensed Unlicensed Requires Authentication Published by De Gruyter September 2, 2014

Legumain expression, activity and secretion are increased during monocyte-to-macrophage differentiation and inhibited by atorvastatin

  • Rigmor Solberg EMAIL logo , Robert Smith , Maria Almlöf , Eyassu Tewolde , Hilde Nilsen and Harald Thidemann Johansen
From the journal Biological Chemistry

Abstract

Macrophages express several lysosomal cysteine proteases such as cathepsins and legumain. In this study, we assessed the expression, activity and secretion of legumain in cellular models of monocytes/macrophages. Macrophages were derived from M-CSF- or GM-CSF/IFNγ-stimulated human primary monocytes (M2 and M1, respectively), PMA-treated human THP-1 cells, or murine RAW264.7 macrophages. In both primary monocytes and THP-1 cells, monocyte-to-macrophage differentiation caused highly increased cellular expression and activity of legumain. Also, secretion of legumain from macrophages, but not from monocytes, was observed. Notably, M2 macrophages expressed significantly higher levels of active legumain than M1 macrophages, which are not previously reported. Legumain mRNA has been shown to be down-regulated in monocytes isolated from patients treated with the HMG-CoA reductase inhibitor atorvastatin. Interestingly, in our study, the active legumain produced by M2 macrophages was found to be inhibited by atorvastatin, which was reflected in aberrant cellular expression and processing.


Corresponding author: Rigmor Solberg, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, Norway, e-mail:

Acknowledgments

The authors would like to thank Magnus Abrahamson for the quantification of cystatin E/M and Anny Thi Tran for technical assistance. This study was supported by The University of Oslo, Anders Jahres foundation for the Promotion of Science, and Astrid and Birger Torsteds Foundation.

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Supplemental Material: The online version of this article (DOI: 10.1515/hsz-2014-0172) offers supplementary material, available to authorized users.Search in Google Scholar


Supplemental Material

The online version of this article (DOI: 10.1515/hsz-2014-0172) offers supplementary material, available to authorized users.


Received: 2014-3-20
Accepted: 2014-6-25
Published Online: 2014-9-2
Published in Print: 2015-1-1

©2014 by De Gruyter

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