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

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.

DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis

“…2f). Moreover, others have previously observed that 1G244, like Val-boroPro, induces cell death in J774 cells 26 . We then treated THP-1 monocytes with sgRNAs to both DPP8 and DPP9 and isolated double knockout cells (Fig.…”

Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non‐small cell lung cancer (NSCLC)

“…DPP9 has two forms and a broad tissue distribution 12. Waumans et al 24. reported that DPP9 expression was relatively low in mouse monocytes and macrophages.…”

Dipeptidyl Peptidase-IV Inhibition for the Treatment of Cardiovascular Disease ― Recent Insights Focusing on Angiogenesis and Neovascularization ―

“…10-12 Recently, Waumans and colleagues clearly demonstrated that among the DPP-IV family members, DPP-VIII and IX inhibition attenuated M1 macrophage activation in mice. 13 Moreover, it was reported that DPP-VIII and IX inhibition induced pro-caspase-1-dependent monocyte and macrophage pyroptosis. 14 These activities confer a broad range of molecular functions on the DPP family, with clinical implications for a potential pathological role in inflammatory and metabolic diseases.…”