Redox regulation of interleukin-8 expression in MKN28 cells.

Recent evidence suggests a role of reactive oxygen intermediates (ROI) in intracellular signaling and regulation of gene expression. We examined whether expression of interleukin-8 (IL-8), a key cytokine in the inflammatory responses of gastric epithelial cells, is sensitive to antioxidants and oxidative stress. IL-8 secretion was quantified by IL-8 enzyme-linked immunosorbent assay, and IL-8 mRNA expression was determined by northern blot analysis. Electrophoretic mobility shift assay was performed to detect the transcription factor, nuclear factor kappaB (NF-kappaB). N-Acetylcysteine (NAC) or dimethylsulfoxide inhibited IL-8 expression induced by tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta). Externally applied H2O2 significantly up-regulated IL-8 expression. TNF-alpha-induced activation of NF-kappaB activity was suppressed by NAC, and H2O2 caused significant activation of NF-kappaB. Since ROI production is increased in the inflamed gastric mucosa, for example, in H. pylori-associated gastritis, the present results suggest that ROI may be an important modulator of IL-8 expression in gastric mucosal cells.