Synergistic effect of tumor necrosis factor-alpha and hydrogen peroxide on the induction of IL-8 production in human intestinal Caco-2 cells.

Oxidative stress and inflammatory cytokines such as TNF-α are thought to be involved in mucosal inflammation. The intestinal epithelium may be concurrently stimulated by both oxidative stress and inflammatory cytokines during the inflammation process in the intestines. However, experimental models for intestinal inflammation still employ single stimulation, either by an oxidative stress or inflammatory cytokine. We therefore examined an in vitro inflammation study using human intestinal epithelial Caco-2 cells, in which the cells were stimulated both by hydrogen peroxide and TNF-α, and measured the IL-8 production as an index of inflammation. The IL-8 production (secretion, mRNA expression, and transcriptional activity) induced by both TNF-α and H(2)O(2) was significantly higher than that by single stimulation. The synergistic effect of TNF-α and H(2)O(2) on the NF-κB signaling pathway (transcriptional activity and p65 nuclear translocation) was also observed. Oxidative stress and TNF-α may cooperatively enhance IL-8 production via NF-κB in Caco-2 cells.