Inhibition of phorbol ester-induced cellular adhesion by competitive binding of NF-κB in vivo

Adhesive interactions between cells are essential for the organization and function of differentiated tissues and organs and are mediated by inducible cell surface glycoproteins. In normal tissues, cell adhesion molecules contribute to immune regulation, inflammation, and embryogenesis. Additionally, they play an important role in a variety of pathogenic processes. Cell adhesion molecule expression can be induced by stimuli known to activate NF-κB, a ubiquitous transcription factor found in a variety of cell types. To investigate the role of NF-κB in cell adhesion molecule expression, we treated HL-60 cells with a double-stranded oligonucleotide which specifically inhibits NF-κB-mediated transcription. This treatment resulted in the inhibition of phorbol 12-myristate 13-acetate (PMA)-induced cellular adhesion, morphological changes, and the expression of leukocyte integrin CD11b. In a similar fashion, expression of intercellular adhesion molecule 1 on human endothelial cells induced by PMA was specifically inhibited by the NF-κB antagonist. We suggest that NF-κB activation is a necessary event for the PMA-induced differentiation of HL-60 cells and the expression of certain adhesion molecules. Furthermore, the inhibition of transcription factor functions by this generally applicable mechanism can be used to define their role in cellular differentiation and function.