Genipin Selectively Inhibits TNF-alpha-activated VCAM-1 But Not ICAM-1 Expression by Upregulation of PPAR-gamma in Human Endothelial Cells.
10.4196/kjpp.2011.15.3.157
- Author:
Jung Seok HWA
1
;
Lidiya MUN
;
Hye Jung KIM
;
Han Geuk SEO
;
Jae Heun LEE
;
Jong Hwan KWAK
;
Dong Ung LEE
;
Ki Churl CHANG
Author Information
1. Department of Urology, School of Medicine, and Institute of Health Sciences, Gyeongsang National University, Jinju 660-290, Korea.
- Publication Type:Original Article
- Keywords:
Atherosclerosis;
Adhesion molecules;
Peroxisome proliferator-activated receptor;
Endothelial cells;
Tumor necrosis factor
- MeSH:
Atherosclerosis;
Cell Adhesion;
Endothelial Cells;
Human Umbilical Vein Endothelial Cells;
Humans;
Inflammation;
Intercellular Adhesion Molecule-1;
Iridoids;
Peroxisomes;
Phosphorylation;
Reactive Oxygen Species;
Risk Factors;
Tumor Necrosis Factor-alpha;
Up-Regulation;
Vascular Cell Adhesion Molecule-1
- From:The Korean Journal of Physiology and Pharmacology
2011;15(3):157-162
- CountryRepublic of Korea
- Language:English
-
Abstract:
Vascular inflammation process has been suggested to be an important risk factor in the development of atherosclerosis. Recently we reported that induction of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) selectively inhibits vascular cell adhesion molecule-1 (VCAM-1) but not intercellular cell adhesion molecule-1 (ICAM-1) in tumor necrosis factor (TNF)-alpha-activated human umbilical vein endothelial cells (HUVEC). In this study, we investigated whether genipin inhibits expression of cellular adhesion molecules, which is relevant to inflammation. Pretreatment with genipin reduced reactive oxygen species (ROS) production and expression of VCAM-1, but not ICAM-1 in TNF-alpha-activated HUVEC. Genipin dose- and time-dependently increased PPAR-gamma expression and inhibited TNF-alpha-induced phosphorylation of Akt and PKC with different degrees. Finally, genipin prevented TNF-alpha-induced adhesion of U937 monocytic cells to HUVEC. Taken together, these results indicate that upregualtion of PPAR-gamma by genipin selectively inhibits TNF-alpha-induced expression of VCAM-1, in which regulation of Akt and/or PKC play a key role. We concluded that genipin can be used for the treatment of cardiovascular disorders such as atherosclerosis.
