Oxidative stress up-regulates IL-8 and TNF-alpha 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-alpha 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.
Verhasselt
V
V
Laboratory of Experimental Immunology, Université Libre de Bruxelles, Brussels, Belgium.
Goldman
M
M
Willems
F
F
D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation
D016207:Cytokines; D006684:HLA-DR Antigens; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide