NF-kappaB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1beta, TNF-alpha, and LPS

J Leukoc Biol. 2000 Apr;67(4):577-84. doi: 10.1002/jlb.67.4.577.


Fractalkine is an endothelial cell-derived CX3C chemokine that is chemotactic mainly to mononuclear cells. Fractalkine was induced in rat aortic endothelial cells (RAEC) by interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-kappaB DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-kappaB subunits p50 and p65 were responsible for kappaB binding. Accordingly, we examined the role of NF-kappaB in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IkappaB as a specific inhibitor. Delivery of a dominant-negative form of IkappaBalpha in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-kappaB activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-kappaB inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-kappaB in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta
  • Cells, Cultured
  • Chemokine CX3CL1
  • Chemokines, CX3C*
  • Chemokines, CXC / biosynthesis*
  • Endothelium, Vascular / metabolism*
  • Interleukin-1 / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Membrane Proteins / biosynthesis*
  • NF-kappa B / metabolism*
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation / drug effects


  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Chemokines, CXC
  • Cx3cl1 protein, rat
  • Interleukin-1
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha