Linagliptin Has Wide-Ranging Anti-Inflammatory Points of Action in Human Umbilical Vein Endothelial Cells

Yuya Nakamura ； Masahiro Inagaki ； Mayumi Tsuji ； Toshihiko Gocho ； Kazuaki Handa ； Hitomi Hasegawa ； Akihiko Yura ； Tomoko Kawakami ； Isao Ohsawa ； Yoshikazu Goto ； Hiromichi Gotoh ； Yuji Kiuchi

《Japanese Clinical Medicine》 2016 (2016/12) Pp. 27-32

https://doi.org/10.4137/JCM.S39317

摘要

BACKGROUND: Because of the potential anti-inflammatory effects, linagliptin, a therapeutic dipeptidyl peptidase-4 inhibitor, is used as an effective drug for diabetic patients for whom inflammation is a prognosis-related factor. We investigated the anti-inflammatory mechanism of linagliptin using seven markers. METHODS: We pretreated human umbilical vein endothelial cells (HUVECs), with linagliptin and lipopolysaccharide (LPS). The cytosolic fractions were evaluated for protein kinase A (PKA), protein kinase B (PKB), protein kinase C (PKC), ratio of reactive oxygen species (ROS) and Cu/Zn superoxide dismutase (SOD), activator protein 1 (AP-1), and adenosine 3',5'-cyclic monophosphate (cAMP). RESULTS: Linagliptin increased the PKA and PKC activities and the cAMP levels in LPS-treated cells. However, it inhibited LPS-induced PKB phosphorylation, ratio of ROS and Cu/Zn SOD, and LPS-stimulated AP-1 nuclear translocation. CONCLUSION: We reaffirmed the anti-inflammatory and antioxidant effects of linagliptin. These effects might be related to the three protein kinases. Our findings suggest that linagliptin has a wide range of anti-inflammatory effects.

關鍵字

linagliptin ； protein kinase ； oxidative stress ； activator protein 1 ； adenosine 3',5'-cyclic monophosphate ； human umbilical vein endothelial cells