Expression and Activation of NF-κB in the Antrum of the Human Stomach

Abstract

Both in vitro studies and experiments in mice suggest a key role for transcription factor NF-κB as a mediator of mucosal inflammation. Experiments in vitro show that NF-κB activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. This study examines the expression and activity of NF-κB in situ in antral biopsies of 69 consecutive patients with immunohistochemical techniques. In the uninflamed stomach, NF-κB was highly expressed and active in a subset of epithelial cells, which were identified as predominantly G cells. In accordance with this activity, G cells were shown to express high levels of the NF-κB target cytokine TNF-α, a well-documented stimulator of gastrin production. In patients with H. pylori-associated gastritis, NF-κB activity was markedly enhanced. Activation occurred preferentially in the epithelial cells. The number of cells showing activated NF-κB correlated with the activity of gastritis, a measure of neutrophil influx, whereas no correlation was found with the chronicity of inflammation, a measure of the presence of mononuclear inflammatory cells. This correlation is direct evidence of the importance of NF-κB-dependent signal transduction for neutrophil influx in H. pylori-associated gastritis.