Distinct signal transduction pathways mediate nuclear factor-kappaB induction by IL-1beta in epithelial and lymphoid cells.
We previously demonstrated that IL-1beta-mediated induction of the nuclear factor-kappaB (NF-kappaB) transcription factor proceeds through the production of reactive oxygen intermediates in lymphoid cells, while it occurs independently of any oxidative stress in epithelial transformed cells. Indeed, inhibition of receptor internalization as well as NH4Cl and chloroquine blocked IL-1beta-mediated induction of NF-kappaB in OVCAR-3 and in other epithelial cell lines but not in lymphoid cells, indicating that distinct pathways are involved. Conversely, while we observed phospholipase A2 activity in both cell types following IL-1beta stimulation, specific inhibitors of this enzyme inhibited NF-kappaB induction only in lymphoid cells. Moreover, expression of the 5-lipoxygenase (5-LOX) enzyme was not detected in epithelial cells, and inhibition of this enzyme blocked NF-kappaB induction by IL-1beta only in lymphoid cells. This study thus indicates that the activation of NF-kappaB following IL-1beta treatment involves the activation of phospholipase A2 and 5-LOX and the production of reactive oxygen intermediates (ROIs) in lymphoid cells, while in epithelial cells, another pathway predominates and could involve the acid sphingomyelinase. Moreover, arachidonic acid could induce NF-kappaB in epithelial and lymphoid cells, but this activation involved the 5-LOX enzyme and the production of ROIs only in lymphoid cells. The inefficiency of the ROI pathway in epithelial cells is probably the consequence of both low ROI production due to undetectable expression of 5-LOX and rapid degradation of hydrogen peroxide due to high catalase activity.
Bonizzi
G
G
Laboratory of Medical Chemistry/Medical Oncology, University of Liege, Belgium.
Piette
J
J
Merville
M P
MP
Bours
V
V
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002518:Ceramides; D007375:Interleukin-1; D016328:NF-kappa B; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D013108:Sphingomyelin Phosphodiesterase