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

Abstract
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.

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