NF-kappaB is required for TNF-alpha-directed smooth muscle cell migration

FEBS Lett. 2001 Nov 23;508(3):360-4. doi: 10.1016/s0014-5793(01)03109-x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Autocrine Communication
  • Cell Movement
  • Cells, Cultured
  • Chemotaxis*
  • Cycloheximide / pharmacology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dactinomycin / pharmacology
  • Genetic Vectors
  • Humans
  • I-kappa B Proteins*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Interleukin-8 / pharmacology
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • NFKBIA protein, human
  • Nucleic Acid Synthesis Inhibitors
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Dactinomycin
  • Cycloheximide