Redox regulation of interleukin-8 expression in MKN28 cells

• Published in: Digestive diseases and sciences 1999-02, Vol.44 (2), p.266-273
• Main Authors: SHIMADA, T, WATANABE, N, HIRAISHI, H, TERANO, A
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Biological and medical sciences; Blotting, Northern; Dimethyl Sulfoxide - pharmacology; Electrophoresis; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Gastric Mucosa - metabolism; Humans; Hydrogen Peroxide - pharmacology; Interleukin-1 - pharmacology; Interleukin-8 - biosynthesis; NF-kappa B - pharmacology; Oxidation-Reduction; Reactive Oxygen Species - metabolism; RNA, Messenger - analysis; Stomach; Transcription Factors - analysis; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; Vertebrates: digestive system
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1023/A:1026638014062

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.