PMID: 9548465Apr 21, 1998Paper

Distinct signal transduction pathways mediate nuclear factor-kappaB induction by IL-1beta in epithelial and lymphoid cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
G BonizziVincent Bours

Abstract

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 sphingomyelinas...Continue Reading

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