Oxidative stress up-regulates IL-8 and TNF-α synthesis by human dendritic cells

In addition to their damaging effects, reactive oxygen intermediates exert a regulatory role on gene expression and cell apoptosis. In this study, we evaluated the effects of oxidative stress on human dendritic cells (DC), a cell type which is critical for the initiation of the immune response. For this purpose, we tested the effects of H₂O₂ on DC derived from adherent peripheral blood mononuclear cells cultured in the presence of granulocyte-macrophage colony-stimulating factor and IL-4. Despite a moderate increase of DC apoptosis in the presence of H₂O₂, we observed that H₂O₂ stimulated the production of IL-8 and TFN-α by DC in a dose-dependent manner. The induction of cytokine synthesis was found to depend on the oxidative properties of H₂O₂ as it was inhibited by the addition of catalase, and to require de novo protein synthesis as it was not observed in the presence of cycloheximide. These data suggest that DC could contribute to innate immunity through an enhanced production of inflammatory cytokines in response to oxidative stress.