Background and Aims: Nuclear translocation of the NF-κB 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 IκB, a family of proteins degraded in response to immunologic and oxidant stimuli. The aim of this study was to examine this mechanism of NF-κB activation in intestinal epithelial cells. Methods: DLD- 1 cell monolayers stimulated by interleukin (IL)-1β or phorbol myristate acetate (PMA) were assayed for the nuclear translocation of NF-κB and immunoreactivity of various IκB isoforms that regulate NF-κB1/RelA activation. Results: NF-κB activation triggered by PMA was not associated with the disappearance of immunoreactive IλBα, IκBβ, IκBγ, or IκBε or with the dissociation of intact IκB from RelA. NF-κB 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-lβ-induced NF-κB activation was associated with the disappearance of IκBα and was inhibited by ALLN but not staurosporine. Conclusions: Our data imply the existence of a novel pathway of NF-κB activation mediated by protein kinase C that does not require proteosomal degradation or the loss of IκB.
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