The role of reactive oxygen intermediates (ROIs) in nuclear factor- kappaB (NF-κB) activation remains a matter of controversy. We have studied whether ROIs played any role in NF-κB induction by interleukin-1β (IL-1β) in different cell types. Our studies indicated three different pathways. IL- 1β stimulation of lymphoid cells generates ROIs, which are required for IκB-α degradation and NF-κB activation. The source of these ROIs is the 5- lipoxygenase (5-LOX) enzyme. In monocytic cells, ROIs are also produced in response to IL-1β and necessary for NF-κB induction, but their source appears to be the NADPH oxidase complex. Finally, epithelial cells do not generate ROIs after IL-1β stimulation, but do rapidly activate NF-κB. Interestingly, transfection of epithelial cells with the 5-LOX and 5-LOX activating protein expression vectors restored ROI production and ROI- dependent NF-κB activation in response to IL-1β. Our data thus indicate that ROIs are cell type-specific second messengers for NF-κB induction by IL-1β.
- Reactive oxygen species
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