J Korean Diabetes Assoc.  2005 Sep;29(5):409-417.

Alpha-Lipoic acid Inhibits TNF-alpha-Induced Fractalkine Expression in Rat aortic Smooth Muscle Cells

Affiliations
  • 1Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
  • 2Department of Pediatrics, Keimyung University School of Medicine, Daegu, Korea.
  • 3Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.

Abstract

BACKGOUND: The induction of vascular inflammation via the proinflammatory cytokine/ nuclear factor (NF)-kappaB pathway is one of the key mechanisms in the development and progression of atherosclerosis. Accumulating evidence suggests a recently identified chemokine, fractalkine, is involved in arterial inflammation and atherogenesis; however, few studies have examined the effects of pharmacological agents on this process. The purposes of this study were to determine if alpha-lipoic acid (ALA) inhibits the expression of tumor necrosis factor (TNF)-alpha-stimulated fractalkine in vascular smooth muscle cells(VSMCs).
METHODS
Rat VSMCs were isolated and cultured. Northern and Western blot analyses were performed to evaluate the effects of ALA on the expression of TNF-alpha-stimulated fractalkine in VSMCs. A gel shift assay was performed to examine the mechanism by which ALA inhibits the expression of fractalkine.
RESULTS
TNF-alpha markedly induced the expression of fractalkine in primary cultured VSMCs. ALA inhibited the expression of TNF-alpha-stimulated fractalkine in cultured VSMCs. The result of the gel shift assay suggested the inhibitory effects of AS-6 on the expression of TNF-alpha-stimulated fractalkine were mediated via the NF-kappaB pathway.
CONCLUSION
This study has shown that ALA has anti-inflammatory effects on VSMCs, which are mediated by the inhibitoin, at least in part, of the NF-kappaB dependent inflammatory signal-stimulated expression of fractalkine. Our data suggest the possibility that antioxidants, such as ALA, inhibit the NF-kappaB pathway, which may be used to prevent the development and progression of atherosclerosis.

Keyword

Alpha-lipoic acid; Atherosclerosis; Fractalkine; NF-kappaB; Vascular smooth muscle cell

MeSH Terms

Animals
Antioxidants
Arteritis
Atherosclerosis
Blotting, Western
Chemokine CX3CL1*
Inflammation
Muscle, Smooth*
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle*
NF-kappa B
Rats*
Thioctic Acid*
Tumor Necrosis Factor-alpha
Antioxidants
Chemokine CX3CL1
NF-kappa B
Thioctic Acid
Tumor Necrosis Factor-alpha
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