The involvement of dipeptidyl peptidase 9 and family members in the immune response and protein turnover
8 May 2015
UAntwerp, Campus Drie Eiken, Promotiezaal - Universiteitsplein 1 - 2610 Wilrijk
4:00 PM - 6:00 PM
Ingrid De Meester
PhD defence Yannick Waumans - Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Department Pharmaceutical Sciences
Dipeptidyl peptidase (DPP) 9 is a prolyl-specific peptidase and is localized in the cytoplasm. DPP9 may play an important role in the immune system. In this thesis we provide a comprehensive review on the DPP family in the immune system and its disorders. We show that DPP9 plays a role in macrophage activation in humans. Selective silencing of DPP9 before macrophage activation attenuates secretion of pro-inflammatory cytokines TNFα and IL-6. Based on our findings we suggest a mechanism of action. Macrophages play an important role in atherosclerosis.
Therefore, we propose DPP9 as a therapeutic target for the prevention and treatment of atherosclerosis. Moreover, literature shows that other DPP family members may be potential targets as well. Our results on DPP9 and its family members in mouse monocytes and macrophages led us to conclude that the mouse may become a valuable model species for the study of the DPPs as therapeutic targets in atherosclerosis. Finally we show that DPP9 and the proteasome colocalize. PREP, another family member of DPP9, colocalizes with the proteasome, as well as with HSP70. Therefore we conclude that the role of these enzymes in protein turnover should not be overlooked.