Oxidant-Induced Activation of Nuclear Factor-Kappa B in Cultured Guinea Pig Gastric Epithelial Cells

The aim of this study was to revealoxidant-sensitive components in gastric epithelialcells, which may regulate inflammatory processes ingastric mucosa. Gel mobility shift assay showed thattreatment of cultured guinea pig gastric epithelial cellswith hydrogen peroxide or diamide produced a κBoligonucleotide-protein complex within 5 min. Thebinding proteins consisted of a p50/p65 heterodimer, which was identified by immunosupershift, UVcrosslinking, and immunoprecipitation analyses.Immunocytochemical study demonstrated that surfaceepithelial cells and parietal cells expressed p50 andp65 mainly in the cytosol, and the oxidants rapidlyinitiated the nuclear translocation of the components.The oxidants caused the up-regulation of p105 (a p50precursor) synthesis and the expression of inducible nitric oxide synthase mRNA. These resultssuggest that the oxidant-sensitive p50/p65 heterodimerin gastric epithelial cells may play an important rolein transcriptional activation of genes involved in inflammatory responses of thestomach.