Cell type-specific role for reactive oxygen species in nuclear factor-kappaB activation by interleukin-1

The role of reactive oxygen intermediates (ROIs) in nuclear factor-kappaB (NF-kappa`) activation remains a matter of controversy. We have studied whether ROIs played any role in NF-kappa B induction by interleukin-1 beta (IL-1 beta) in different cell types. Our studies indicated three different pathways. IL-1 beta stimulation of lymphoid cells generates ROIs, which are required for I kappa B-alpha degradation and NF-kappa B activation. The source of these ROIs is the 5 lipoxygenase (5-LOX) enzyme. In monocytic cells, ROIs are also produced in response to IL-1 beta and necessary for NF-kappa B induction, but their source appears to be the NADPH oxidase complex. Finally, epithelial cells do not generate ROIs after IL-1 beta stimulation, but do rapidly activate NF-kappa B. Interestingly, transfection of epithelial cells with the 5-LOX and 5-LOX activating protein expression vectors restored ROI production and ROI-dependent NF-kappa B activation in response to IL-1 beta. Our data thus indicate that ROIs are cell type-specific second messengers for NF-kappa B induction by IL-1 beta. BIOCHEM PHARMACOL 59;1:7-11, 2000. (C) 1999 Elsevier Science Inc.