PMID- 16989870
OWN - NLM
STAT- MEDLINE
DCOM- 20070206
LR  - 20171116
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 80
IP  - 2
DP  - 2006 Dec 14
TI  - The ascochlorin derivative, AS-6, inhibits TNF-alpha-induced adhesion molecule 
      and chemokine expression in rat vascular smooth muscle cells.
PG  - 120-6
AB  - Vascular inflammation induced by the proinflammatory cytokine/NF-kappaB pathway 
      is one of the key mechanisms in the development of atherosclerosis. Peroxisome 
      proliferators-activated receptor-gamma (PPARgamma) plays an important role in the 
      prevention of arterial inflammation and formation of atherogenesis. Herein we 
      examine the effects of a newly identified synthetic PPARgamma ligand, 
      ascochlorin-6 (AS-6), on TNF-alpha-stimulated NF-kappaB activity and inflammatory 
      molecule expression in vascular smooth muscle cells (VSMCs). AS-6 successfully 
      inhibited TNF-alpha-stimulated NF-kappaB 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-kappaB]x4 luciferase reporter construct showed that AS-6 inhibition 
      of TNF-alpha-stimulated NF-kappaB activation was PPARgamma-dependent. The effects 
      of AS-6 on TNF-alpha-stimulated VCAM-1 and CX3CL1 expression were abolished in 
      cells transfected with an adenovirus expressing dominant-negative PPARgamma and 
      in cells treated with a PPARgamma specific inhibitor, GW9662, confirming again 
      that the anti-inflammatory effect of AS-6 was PPARgamma-dependent. The inhibitory 
      effects of AS-6 on TNF-alpha-stimulated inflammatory gene expression and 
      NF-kappaB activation were more potent than those of rosiglitazone and 
      pioglitazone. This study shows that AS-6 reduces the inflammatory response to 
      TNF-alpha in VSMCs. The data suggest the possibility that AS-6 can be used to 
      prevent the development and progression of atherosclerosis.
FAU - Park, Keun-Gyu
AU  - Park KG
AD  - Department of Internal Medicine and Institute for Medical Science, Keimyung 
      University School of Medicine, Daegu, South Korea.
FAU - Lee, Kyeong-Min
AU  - Lee KM
FAU - Chang, Young-Chae
AU  - Chang YC
FAU - Magae, Junji
AU  - Magae J
FAU - Ando, Kunio
AU  - Ando K
FAU - Kim, Kwon-Bae
AU  - Kim KB
FAU - Kim, Yoon-Nyun
AU  - Kim YN
FAU - Kim, Hye-Soon
AU  - Kim HS
FAU - Park, Joong-Yeol
AU  - Park JY
FAU - Lee, Ki-Up
AU  - Lee KU
FAU - Lee, In-Kyu
AU  - Lee IK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060901
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Alkenes)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CX3CL1)
RN  - 0 (Chemokines, CX3C)
RN  - 0 (Cx3cl1 protein, rat)
RN  - 0 (Glycolates)
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR gamma)
RN  - 0 (Phenols)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - I1BK0ZE06X (4-O-carboxymethylascochlorin)
RN  - PEZ8F05ODV (ascochlorin)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Alkenes/*chemistry
MH  - Animals
MH  - Aorta, Thoracic/cytology
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CX3CL1
MH  - Chemokines, CX3C/*biosynthesis/genetics
MH  - Gene Expression/drug effects
MH  - Genetic Vectors
MH  - Glycolates/*pharmacology
MH  - Ligands
MH  - Male
MH  - Membrane Proteins/*biosynthesis/genetics
MH  - Muscle, Smooth, Vascular/*cytology
MH  - NF-kappa B/metabolism
MH  - PPAR gamma/genetics/*metabolism
MH  - Phenols/*chemistry
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/genetics/metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vascular Cell Adhesion Molecule-1/*biosynthesis/genetics
EDAT- 2006/09/23 09:00
MHDA- 2007/02/07 09:00
CRDT- 2006/09/23 09:00
PHST- 2006/02/07 00:00 [received]
PHST- 2006/07/03 00:00 [revised]
PHST- 2006/08/23 00:00 [accepted]
PHST- 2006/09/23 09:00 [pubmed]
PHST- 2007/02/07 09:00 [medline]
PHST- 2006/09/23 09:00 [entrez]
AID - S0024-3205(06)00660-6 [pii]
AID - 10.1016/j.lfs.2006.08.030 [doi]
PST - ppublish
SO  - Life Sci. 2006 Dec 14;80(2):120-6. doi: 10.1016/j.lfs.2006.08.030. Epub 2006 Sep 
      1.