Protein kinase C-dependent activation of NF-kappaB in enterocytes is independent of IkappaB degradation.
OBJECTIVE
Nuclear translocation of the NF-kappaB family of transcription factors is a proximal step in the signal transduction of a pleiotropic group of proinflammatory genes. Activation of RelA is under the negative control of IkappaB, a family of proteins degraded in response to immunologic and oxidant stimuli. The aim of this study was to examine this mechanism of NF-kappaB activation in intestinal epithelial cells.


METHODS
DLD-1 cell monolayers stimulated by interleukin (IL)-1beta or phorbol myristate acetate (PMA) were assayed for the nuclear translocation of NF-kappaB and immunoreactivity of various IkappaB isoforms that regulate NF-kappaB1/RelA activation.


RESULTS
NF-kappaB activation triggered by PMA was not associated with the disappearance of immunoreactive IkappaBalpha, IkappaBbeta, IkappaBgamma, or IkappaBepsilon or with the dissociation of intact IkappaB from RelA. NF-kappaB 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-1beta-induced NF-kappaB activation was associated with the disappearance of IkappaBalpha and was inhibited by ALLN but not staurosporine.


CONCLUSIONS
Our data imply the existence of a novel pathway of NF-kappaB activation mediated by protein kinase C that does not require proteosomal degradation or the loss of IkappaB.
Wilson
L
L
Division of Critical Care, Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Szabó
C
C
Salzman
A L
AL
D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D007700:Kinetics; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D007375:Interleukin-1; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate