NF-κB is required for TNF-α-directed smooth muscle cell migration

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, 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 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. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.