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The ascochlorin derivative, AS-6, inhibits TNF-α-induced adhesion molecule and chemokine expression in rat vascular smooth muscle cells

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Affiliated Author(s)
박근규김권배김윤년김혜순
Alternative Author(s)
Park, Keun GyuKim, Kwon BaeKim, Yoon NyunKim, Hye Soon
Journal Title
Life Science
ISSN
0024-3205
Issued Date
2006
Keyword
Ascochlorin-6AtherosclerosisCX3CL1MCP-1PPARγVascular smooth muscle cellVCAM-1
Abstract
Vascular inflammation induced by the proinflammatory cytokine/NF-κB pathway is one of the key mechanisms in the development of atherosclerosis. Peroxisome proliferators-activated receptor-γ (PPARγ) plays an important role in the prevention of arterial inflammation and formation of atherogenesis. Herein we examine the effects of a newly identified synthetic PPARγ ligand, ascochlorin-6 (AS-6), on TNF-α-stimulated NF-κB activity and inflammatory molecule expression in vascular smooth muscle cells (VSMCs). AS-6 successfully inhibited TNF-α-stimulated NF-κB activity and inflammatory molecule expression, including vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1), and fractalkine (CX3CL1). Transient transfection with an [NF-κB]×4 luciferase reporter construct showed that AS-6 inhibition of TNF-α-stimulated NF-κB activation was PPARγ-dependent. The effects of AS-6 on TNF-α-stimulated VCAM-1 and CX3CL1 expression were abolished in cells transfected with an adenovirus expressing dominant-negative PPARγ and in cells treated with a PPARγ specific inhibitor, GW9662, confirming again that the anti-inflammatory effect of AS-6 was PPARγ-dependent. The inhibitory effects of AS-6 on TNF-α-stimulated inflammatory gene expression and NF-κB activation were more potent than those of rosiglitazone and pioglitazone. This study shows that AS-6 reduces the inflammatory response to TNF-α in VSMCs. The data suggest the possibility that AS-6 can be used to prevent the development and progression of atherosclerosis.
Department
Dept. of Internal Medicine (내과학)
Institute for Medical Science (의과학연구소)
Publisher
School of Medicine
Citation
Keun-Gyu Park et al. (2006). The ascochlorin derivative, AS-6, inhibits TNF-α-induced adhesion molecule and chemokine expression in rat vascular smooth muscle cells. Life Science, 80(2), 120–126. doi: 10.1016/j.lfs.2006.08.030
Type
Article
ISSN
0024-3205
DOI
10.1016/j.lfs.2006.08.030
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36301
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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