Different modes of NF-κB/Rel activation in pancreatic lobules

The eukaryotic transcription factor nuclear factor-κB (NF-κB)/Rel is activated by a large variety of stimuli. It has been demonstrated that NF-κB/Rel is induced during the course of cerulein pancreatitis. Here, we show that NF-κB/Rel is differentially activated in pancreatic lobules. Cerulein induces NF-κB/Rel via activation of IκB kinase (IKK), which causes degradation of IκBα but not IκBβ. Tumor necrosis factor-α-mediated IKK activation leads to IκBα and IκBβ degradation. In contrast, oxidative stress induced by H₂O₂ activates NF-κB/Rel independent of IKK activation and IκBα degradation; instead IκBα is phosphorylated on tyrosine. H₂O₂ but not cerulein-mediated NF-κB/Rel activation can be blocked by stabilizing microtubules with Taxol. Inhibition of tubulin polymerization with nocodazole causes NF-κB/Rel activation in pancreatic lobules. These results propose three different pathways of NF-κB/Rel activation in pancreatic acinar cells. Furthermore, these data demonstrate that microtubules play a key role in IKK-independent NF-κB/Rel activation following oxidative stress.