title: 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.
authors.affiliation: Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Waumans
authors.affiliation: Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Vliegen
authors.affiliation: Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.
authors.forename: Lynn
authors.initials: L
authors.lastname: Maes
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Miche
authors.initials: M
authors.lastname: Rombouts
authors.affiliation: Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), University of Antwerp, Antwerp, Belgium.
authors.forename: Ken
authors.initials: K
authors.lastname: Declerck
authors.affiliation: Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Der Veken
authors.affiliation: Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), University of Antwerp, Antwerp, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Vanden Berghe
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Guido R Y
authors.initials: GRY
authors.lastname: De Meyer
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Dorien
authors.initials: D
authors.lastname: Schrijvers
authors.affiliation: Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium. ingrid.demeester@uantwerpen.be.
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Meester
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse; C585325:dipeptidyl peptidase 8, mouse; C585326:dipeptidyl peptidase 9, mouse
keywords: DPP4; atherosclerosis; dipeptidyl peptidase; macrophages; monocytes