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

Overview

Journal Jpn Clin Med

Publisher Sage Publications

Specialty General Medicine

Date 2016 Dec 17

PMID 27980448

Citations 7

Authors

Yuya Nakamura

Masahiro Inagaki

Mayumi Tsuji

Toshihiko Gocho

Kazuaki Handa

Hitomi Hasegawa

Akihiko Yura

Tomoko Kawakami

Isao Ohsawa

Yoshikazu Goto

Hiromichi Gotoh

Yuji Kiuchi

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Ameliorates Endothelial Inflammation and Microvascular Thrombosis in a Sepsis Mouse Model.

Wang S, Wang X, Liu C, Chou R, Chen Z, Huang P Int J Mol Sci. 2022; 23(6).

PMID: 35328486 PMC: 8949150. DOI: 10.3390/ijms23063065.

Linagliptin Inhibits Interleukin-6 Production Through Toll-Like Receptor 4 Complex and Lipopolysaccharide-Binding Protein Independent Pathway in vitro Model.

Saito H, Nakamura Y, Inagaki M, Yamadera S, Misawa H, Sato N J Inflamm Res. 2021; 14:5681-5686.

PMID: 34754214 PMC: 8572089. DOI: 10.2147/JIR.S326382.

Effects of Incretin-Related Diabetes Drugs on Bone Formation and Bone Resorption.

Kitaura H, Ogawa S, Ohori F, Noguchi T, Marahleh A, Nara Y Int J Mol Sci. 2021; 22(12).

PMID: 34205264 PMC: 8234693. DOI: 10.3390/ijms22126578.

Effect of a DPP-4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption.

Qi J, Kitaura H, Shen W, Ogawa S, Ohori F, Noguchi T Biomed Res Int. 2020; 2020:7189084.

PMID: 32923485 PMC: 7453249. DOI: 10.1155/2020/7189084.

Linagliptin Inhibits Lipopolysaccharide-Induced Inflammation Concentration-Dependently And -Independently.

Sato N, Nakamura Y, Yamadera S, Inagaki M, Kenmotsu S, Saito H J Inflamm Res. 2019; 12:285-291.

PMID: 31695471 PMC: 6814358. DOI: 10.2147/JIR.S221761.

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