Redox regulation of interleukin-8 expression in MKN28 cells

Recent evidence suggests a role of reactive oxygen intermediates (ROI) in i ntracellular signaling and regulation of gene expression. We examined wheth er expression of interleukin-8 (IL-8), a key cytokine in the inflammatory r esponses of gastric epithelial cells, is sensitive to antioxidants and oxid ative stress. IL-8 secretion was quantified by IL-8 enzyme-linked immunosor bent assay, and IL-8 mRNA expression was determined by northern blot analys is. Electrophoretic mobility shift assay was performed to detect the transc ription factor, nuclear factor kappa B (NF-kappa B). N-Acetylcysteine (NAC) or dimethylsulfoxide inhibited IL-8 expression induced by tumor necrosis f actor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). Externally appli ed H2O2 significantly up-regulated IL-8 expression. TNF-alpha-induced activ ation of NF-kappa B activity was suppressed by NAC, and H2O2 caused signifi cant activation of NF-kappa B. Since ROI production is increased in the inf lamed gastric mucosa, for example, in H. pylori-associated gastritis, the p resent results suggest that ROI may be an important modulator of IL-8 expre ssion in gastric mucosal cells.