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The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice

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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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