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-α (TNF-α) is elaborated by VSMC in atherosclerosis and following angioplasty. We investigated the role of nuclear factor-κB (NF-κB) in human VSMC migration induced by TNF-α. Adenoviral expression of a mutant form of the inhibitor of NF-κB, IκB-αM, suppressed TNF-α-triggered degradation of cellular IκB-α, inhibited activation of NF-κB, and attenuated TNF-α-induced migration. Further, IκB-αM suppressed TNF-α-stimulated release of interleukin-6 and -8 (IL-6 and IL-8). Neutralization of IL-6 and IL-8 with appropriate antibodies reduced TNF-α-induced VSMC migration. Addition of recombinant IL-6 and IL-8 stimulated migration. Collectively, our data provide initial evidence that TNF-α-mediated VSMC migration requires NF-κB activation and is associated with induction of IL-6 and IL-8 which act in an autocrine manner.