Abstract
Atherosclerosis remains the leading cause of death in Western countries. Dipeptidyl peptidase (DPP) 4 has emerged as a novel target for the prevention and treatment of atherosclerosis. Family members DPP8 and 9 are abundantly present in macrophage-rich regions of atherosclerotic plaques, and DPP9 inhibition attenuates activation of human M1 macrophages in vitro. Studying this family in a mouse model for atherosclerosis would greatly advance our knowledge regarding their potential as therapeutic targets. We found that DPP4 is downregulated during mouse monocyte-to-macrophage differentiation. DPP8 and 9 expression seems relatively low in mouse monocytes and macrophages. Viability of primary mouse macrophages is unaffected by DPP4 or DPP8/9 inhibition. Importantly, DPP8/9 inhibition attenuates macrophage activation as IL-6 secretion is significantly decreased. Mouse macrophages respond similarly to DPP inhibition, compared to human macrophages. This shows that the mouse could become a valid model species for the study of DPPs as therapeutic targets in atherosclerosis.
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Abbreviations
- DPP:
-
Dipeptidyl peptidase
- wt:
-
Wild-type
- ApoE−/− :
-
Apolipoprotein E-deficient
- BMDMo:
-
Bone-marrow-derived monocyte
- BMDMφ:
-
Bone-marrow-derived macrophage
- IFN:
-
Interferon
- LPS:
-
Lipopolysaccharide
- IL:
-
Interleukin
- TNF:
-
Tumor necrosis factor
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Acknowledgments
This work was supported by the University of Antwerp (GOA2009-2012 and GOA2015-2018) and the Fund for Scientific Research Flanders (grant nr. G.0141.12). Yannick Waumans is a research assistant of the Fund for Scientific Research Flanders.
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Waumans, Y., Vliegen, G., Maes, L. et al. The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice. Inflammation 39, 413–424 (2016). https://doi.org/10.1007/s10753-015-0263-5
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DOI: https://doi.org/10.1007/s10753-015-0263-5