- Alpha-Lipoic acid Inhibits TNF-alpha-Induced Fractalkine Expression in Rat aortic Smooth Muscle Cells.
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Keun Gyu Park, Hye Soon Kim, Seong Yeol Ryu, Chang Wook Nam, Byung Kyu Chae, Eui Dal Jung, Jung Guk Kim, Bo Wan Kim, In Kyu Lee
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Korean Diabetes J. 2005;29(5):409-417. Published online September 1, 2005
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 Abstract
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- 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.
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KDA
