Migration of vascular smooth muscle cells (VSMC) is a crucial event in the
formation of vascular stenotic lesions. Tumor necrosis factor-alpha (TNF-al
pha) is elaborated by VSMC in atherosclerosis and following angioplasty. We
investigated the role of nuclear factor-kappaB (NF-kappaB) in human VSMC m
igration induced by TNF-alpha. Adenoviral expression of a mutant form of th
e inhibitor of NF-kappaB, I kappaB-alphaM, suppressed TNF-alpha -triggered
degradation of cellular I kappaB-alpha, inhibited activation of NF-kappaB,
and attenuated TNF-alpha -induced migration. Further, I kappaB-alphaM suppr
essed 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-a
lpha -induced VSMC migration. Addition of recombinant IL-6 and IL-8 stimula
ted migration. Collectively, our data provide initial evidence that TNF-alp
ha -mediated VSMC migration requires NF-kappaB activation and is associated
with induction of IL-6 and IL-8 which act in an autocrine manner. (C) 2001
Federation of European Biochemical Societies. Published by Elsevier Scienc
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