L. Wilson et al., Protein kinase C-dependent activation of NF-kappa B in enterocytes is independent of I kappa B degradation, GASTROENTY, 117(1), 1999, pp. 106-114
Background & Aims: Nuclear translocation of the NF-kappa B family of transc
ription factors is a proximal step in the signal transduction of a pleiotro
pic group of proinflammatory genes. Activation of RelA is under the negativ
e control of I kappa B, a family of proteins degraded in response to immuno
logic and oxidant stimuli. The aim of this study was to examine this mechan
ism of NF-kappa B activation in intestinal epithelial cells. Methods: DLD-1
cell monolayers stimulated by interleukin (Il)-1 beta or phorbol myristate
acetate (PMA) were assayed for the nuclear translocation of NF-kappa B and
immunoreactivity of various I kappa B isoforms that regulate NF-kappa B1/R
elA activation. Results: NF-kappa B activation triggered by PMA was not ass
ociated with the disappearance of immunoreactive I kappa B alpha, I kappa B
beta, I kappa B gamma, or I kappa B epsilon or With the dissociation of in
tact I kappa B from RelA. NF-kappa B activation induced by PMA was blocked
by the protein kinase C inhibitor staurosporine but not by the proteasomal
Inhibitor N-acetyl-leucine leucine norleucinal (ALLN). In contrast, IL-1 be
ta-induced NF-kappa B activation was associated with the disappearance of I
kappa B alpha and was inhibited by ALLN but not staurosporine. Conclusions
: Our data imply the existence of a novel pathway of NF-kappa B activation
mediated by protein kinase C that does not require proteosomal degradation
or the loss of I kappa B.