title: 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.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Liang
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Wang
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.forename: Shih-Sheng
authors.initials: SS
authors.lastname: Chang
authors.forename: Tong-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Yann-Lii
authors.initials: YL
authors.lastname: Leu
authors.forename: Ying-Chih
authors.initials: YC
authors.lastname: Tseng
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Li
authors.forename: Yuh-Lien
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050197:Atherosclerosis / Q000517:prevention & control; D001713:Biphenyl Compounds / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D028181:Viscum / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C513809:viscolin; D019255:NADPH Oxidases; D048670:MAP Kinase Kinase 4; D011407:Propane