The dipeptidyl peptidase-IV inhibitor inhibits the expression of vascular adhesion molecules and inflammatory cytokines in HUVECs via Akt- and AMPK-dependent mechanisms
- Authors
- Hwang, Hwan-Jin; Chung, Hye Soo; Jung, Tae Woo; Ryu, Ja Young; Hong, Ho Cheol; Seo, Ji A.; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin
- Issue Date
- 15-4월-2015
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Dipeptidyl peptidase-IV inhibitors; AMP-activated protein kinase; Inflammation; Endothelial cells
- Citation
- MOLECULAR AND CELLULAR ENDOCRINOLOGY, v.405, no.C, pp.25 - 34
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR AND CELLULAR ENDOCRINOLOGY
- Volume
- 405
- Number
- C
- Start Page
- 25
- End Page
- 34
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/93835
- DOI
- 10.1016/j.mce.2015.01.025
- ISSN
- 0303-7207
- Abstract
- Recently, dipeptidyl peptidase-IV (DPP-IV) inhibitor, a major anti-hyperglycemic agent, has received substantial attention as a possible therapeutic target for inflammatory diseases such as atherosclerosis. However, the direct molecular mechanisms through which DPP-IV inhibitor mediates anti-inflammatory effects in vascular endothelial cells have not been clarified. The effects of the DPP-IV inhibitor, gemigliptin, were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Using Western blotting, we demonstrated that gemigliptin efficiently increased the level of AMP-activated protein kinase (AMPK) and Akt phosphorylation in a dose-dependent manner. The levels of lipopolysaccharide (LPS)-mediated phosphorylated nuclear factor-kappa B (NF-kappa B) and c-Jun N-terminal kinase (INK) were significantly decreased after gemigliptin treatment. Furthermore, gemigliptin reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), interleukin-1 beta (IL-1 beta), and IL-6 in HUVECs. In macrophage-like THP-1 cells, gemigliptin effectively inhibited LPS- and low-density lipoprotein (LDL)-induced foam cell formation. However, these anti-inflammatory and antiatherosclerotic effects of gemigliptin in HUVECs and ITIP-1 cells were significantly reduced after treatment with an AMPK or an Akt inhibitor. Our results suggest that gemigliptin efficiently inhibited LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-kappa B and JNK signaling via Akt/AMPK-dependent mechanisms. Therefore, the DPP-IV inhibitor, gemigliptin, may directly protect the vascular endothelium against inflammatory diseases such as atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.