NF-κB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1β, TNF-α, and LPS

Publisher Website
Google Scholar
Abstract
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 interleu-kin-1β (IL-1β), tumor necrosis factor α (TNF-α), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-κB DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-κB subunits p50 and p65 were responsible for κB binding. Accordingly, we examined the role of NF-κB in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IκB as a specific inhibitor. Delivery of a dominant-negative form of IκBα in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-κB activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-κB inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-κB in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction. J. Leukoc. Biol. 67: 577–584; 2000.

This publication has 0 references indexed in Scilit: