Exposure to hydrogen peroxide diminishes NF-κB activation, IκB-α degradation, and proteasome activity in neutrophils

Although ROS can participate in modulating the activity of the transcriptional factor NF-kappa B and expression of NF-kappa B-dependent genes, the mechanisms involved and the roles of specific ROS have not been fully determined. In particular, individual ROS appear to have differing effects on NF-kappa B activation dependent on the cell population studied. In the present study, we examined the ability of H2O2 to affect NF-kappa B activation in LPS-stimulated murine neutrophils and macrophages. Exposure of bone marrow or peritoneal neutrophils to H2O2 was associated with reduced nuclear translocation of NF-kappa B and decreased production of the NF-kappa B-dependent cytokines TNF-alpha and macrophage inhibitory protein-2. H2O2 treatment resulted in diminished trypsin- and chymotrypsinlike proteasome activity. The degradation of I kappa B-alpha normally found in LPS-treated neutrophils was prevented when H2O2 was added to cell cultures. In contrast to the effects found in neutrophils, H2O2 did not affect chymotrypsin- like proteasomal activity or cytokine production in LPS-stimulated macrophages, even though trypsin- like proteasomal activity was reduced. These results demonstrate that the effects of H2O2 on NF-kappa B and proteasomal activity are cell population specific.