Implication of NF-κB in Helicobacter pylori-associated gastritis

OBJECTIVE: Transcription factor NF-kappa B plays a pivotal role in inflammatory responses by up-regulating mRNA expression of bioactive molecules such as chemokines and adhesion molecules. The present study was designed to elucidate the implication of NF-kappa B in Helicobacter pylori-associated gastritis (HAG). METHODS: We examined 41 patients with HAG and 18 H. pylori-negative control subjects. Expression of activated NF-kappa B was studied in situ by immunohistochemistry using alpha-p65 mouse monoclonal antibody (alpha-p65 mAb), which recognizes activated NF-kappa B. To identify the cell types in which NF-kappa B was activated, we performed immunohistochemical analysis using antibodies against vascular endothelial cells, macrophages, and B and T lymphocytes. We also examined the colocalization of activated NF-kappa B with the expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. We measured the levels of NF-kappa B-dependent chemokines including interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in antral mucosa by ELISA (ELISA). RESULTS: Activated NF-kappa B was detected in the nuclei of epithelial cells in antral mucosa, especially of patients with HAG. NF-kappa B positivity index (NF-kappa B PI), representing the percentages of epithelial cells with positive nuclear staining for activated NF-kappa B, was significantly higher in patients with HAG than in H. pylori-negative controls. NF-kappa B PI correlated significantly with histological scores of gastritis. Moreover, activated NF-kappa B was identified in the nuclei of vascular endothelial cells, macrophages, and B lymphocytes within the lamina propria in HAG. Colocalization of activated NF-kappa B with ICAM-1 expression in the same endothelial cells was demonstrated. The IL-8 levels significantly correlated with the NF-kappa B PI. CONCLUSIONS: In addition to epithelial cells, macrophages, vascular endothelial cells, and B lymphocytes contained activated NF-kappa B. In these cells, activated NF-kappa B may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules. (Am J Gastroenterol 2000;95:2768-2776. (C) 2000 by Am. Coll. of Gastroenterology).