Implication of NF-kappa B in Helicobacter pylori-associated gastritis

OBJECTIVE: Transcription factor NF-kappa B plays a pivotal role in inflamma tory responses by up-regulating mRNA expression of bioactive molecules such as chemokines and adhesion molecules. The present study was designed to el ucidate the implication of NF-kappa B in Helicobacter pylori-associated gas tritis (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 immuno histochemistry using alpha-p65 mouse monoclonal antibody (alpha-p65 mAb), w hich recognizes activated NF-kappa B. To identify the cell types in which N F-kappa B was activated, we performed immunohistochemical analysis using an tibodies against vascular endothelial cells, macrophages, and B and T lymph ocytes. We also examined the colocalization of activated NF-kappa B with th e expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial c ells. We measured the levels of NF-kappa B-dependent chemokines including i nterleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), regulat ed on activation normal T-cell expressed and secreted (RANTES) and macropha ge inflammatory protein-1 alpha (MIP-1 alpha) in antral mucosa by ELISA (EL ISA). RESULTS: Activated NF-kappa B was detected in the nuclei of epithelial cell s in antral mucosa, especially of patients with HAG. NF-kappa B positivity index (NF-kappa B PI), representing the percentages of epithelial cells wit h positive nuclear staining for activated NF-kappa B, was significantly hig her 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 c ells, macrophages, and B lymphocytes within the lamina propria in HAG. Colo calization of activated NF-kappa B with ICAM-1 expression in the same endot helial cells was demonstrated. The IL-8 levels significantly correlated wit h the NF-kappa B PI. CONCLUSIONS: In addition to epithelial cells, macrophages, vascular endothe lial cells, and B lymphocytes contained activated NF-kappa B. In these cell s, activated NF-kappa B may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules. (Am J Gastro enterol 2000;95:2768-2776. (C) 2000 by Am. Coll. of Gastroenterology).