Sl. Eck et al., INHIBITION OF PHORBOL ESTER-INDUCED CELLULAR ADHESION BY COMPETITIVE-BINDING OF NF-KB IN-VIVO, Molecular and cellular biology, 13(10), 1993, pp. 6530-6536
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 adhesio
n molecules contribute to immune regulation, inflammation, and embryog
enesis. Additionally, they play an important role in a variety of path
ogenic processes. Cell adhesion molecule expression can be induced by
stimuli known to activate NF-kappaB, a ubiquitous transcription factor
found in a variety of cell types. To investigate the role of NF-kappa
B in cell adhesion molecule expression, we treated HL-60 cells with a
double-stranded oligonucleotide which specifically inhibits NF-kappaB-
mediated transcription. This treatment resulted in the inhibition of p
horbol 12-myristate 13-acetate (PMA)-induced cellular adhesion, morpho
logical changes, and the expression of leukocyte integrin CD11b. In a
similar fashion, expression of intercellular adhesion molecule 1 on hu
man endothelial cells induced by PMA was specifically inhibited by the
NF-kappaB antagonist. We suggest that NF-kappaB activation is a neces
sary 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 mechani
sm can be used to define their role in cellular differentiation and fu
nction.