Viscolin reduces VCAM-1 expression in TNF-α-treated endothelial cells via the JNK/NF-κB and ROS pathway.

Abstract

Viscolin, a major active component in a chloroform extract of Viscum coloratum, has antioxidative and anti-inflammatory properties. We focused on its effects on the expression of vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-α (TNF-α)-treated human umbilical vein endothelial cells (HUVECs). The TNF-α-induced expression of VCAM-1 was significantly reduced by respectively 38±7 or 34±16% when HUVECs were pretreated with 10 or 30μM viscolin, as shown by Western blotting, and was also significantly reduced by pretreatment with the antioxidants N-acetylcysteine, diphenylene iodonium chloride, and apocynin. Viscolin also reduced TNF-α-induced VCAM-1 mRNA expression and promoter activity, decreased reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and significantly reduced the binding of monocytes to TNF-α-stimulated HUVECs. The attenuation of TNF-α-induced VCAM-1 expression and cell adhesion was partly mediated by a decrease in JNK phosphorylation. Furthermore, viscolin reduced VCAM-1 expression in the aorta of TNF-α-treated mice in vivo. Taken together, these data show that viscolin inhibits TNF-α-induced JNK phosphorylation, nuclear translocation of NF-κB p65, and ROS generation and thereby suppresses VCAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that viscolin may prevent the development of atherosclerosis and inflammatory responses.

• Authors: Chan-Jung Liang, Shu-Huei Wang, Yung-Hsiang Chen, Shih-Sheng Chang, Tong-Long Hwang, Yann-Lii Leu, Ying-Chih Tseng, Chi-Yuan Li, Yuh-Lien Chen
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 51 Issue 7 Pg. 1337-46 (Oct 01 2011) ISSN: 1873-4596 [Electronic] United States
• PMID: 21767632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Biphenyl Compounds
• RNA, Messenger
• Reactive Oxygen Species
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• viscolin
• NADPH Oxidases
• MAP Kinase Kinase 4
• Propane

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Aorta (cytology, drug effects, metabolism)
• Atherosclerosis (prevention & control)
• Biphenyl Compounds (pharmacology)
• Blotting, Western
• Cell Adhesion (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation
• Endothelial Cells (cytology, drug effects, metabolism)
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• MAP Kinase Kinase 4 (antagonists & inhibitors, genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Monocytes (drug effects)
• NADPH Oxidases (antagonists & inhibitors, genetics, metabolism)
• Phosphorylation (drug effects)
• Propane (analogs & derivatives, pharmacology)
• RNA, Messenger (analysis)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Transcription Factor RelA (antagonists & inhibitors, genetics, metabolism)
• Tumor Necrosis Factor-alpha (adverse effects, pharmacology)
• Vascular Cell Adhesion Molecule-1 (biosynthesis)
• Viscum (chemistry)