Abstract
Migration of vascular smooth muscle cells (VSMC) is a crucial event in the formation of vascular stenotic lesions. Tumor necrosis factor-alpha (TNF-alpha) is elaborated by VSMC in atherosclerosis and following angioplasty. We investigated the role of nuclear factor-kappaB (NF-kappaB) in human VSMC migration induced by TNF-alpha. Adenoviral expression of a mutant form of the inhibitor of NF-kappaB, IkappaB-alphaM, suppressed TNF-alpha-triggered degradation of cellular IkappaB-alpha, inhibited activation of NF-kappaB, and attenuated TNF-alpha-induced migration. Further, IkappaB-alphaM suppressed TNF-alpha-stimulated release of interleukin-6 and -8 (IL-6 and IL-8). Neutralization of IL-6 and IL-8 with appropriate antibodies reduced TNF-alpha-induced VSMC migration. Addition of recombinant IL-6 and IL-8 stimulated migration. Collectively, our data provide initial evidence that TNF-alpha-mediated VSMC migration requires NF-kappaB activation and is associated with induction of IL-6 and IL-8 which act in an autocrine manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Autocrine Communication
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Cell Movement
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Cells, Cultured
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Chemotaxis*
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Cycloheximide / pharmacology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Dactinomycin / pharmacology
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Genetic Vectors
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Humans
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I-kappa B Proteins*
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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Interleukin-8 / pharmacology
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Muscle, Smooth, Vascular / cytology*
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Muscle, Smooth, Vascular / metabolism*
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism*
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Protein Synthesis Inhibitors / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology*
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Tumor Necrosis Factor-alpha / physiology
Substances
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DNA-Binding Proteins
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I-kappa B Proteins
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Interleukin-6
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Interleukin-8
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NF-kappa B
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NFKBIA protein, human
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Nucleic Acid Synthesis Inhibitors
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Protein Synthesis Inhibitors
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RNA, Messenger
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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NF-KappaB Inhibitor alpha
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Dactinomycin
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Cycloheximide