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

Abstract

Although ROS can participate in modulating the activity of the transcriptional factor NF-κB and expression of NF-κB-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-κB activation dependent on the cell population studied. In the present study, we examined the ability of H₂O₂ to affect NF-κB 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-κB and decreased production of the NF-κB-dependent cytokines TNF-α and macrophage inhibitory protein-2. H₂O₂ treatment resulted in diminished trypsin- and chymotrypsin-like proteasome activity. The degradation of IκB-α 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-κB and proteasomal activity are cell population specific.