Comparison of CXC Chemokines ENA-78 and Interleukin-8 Expression in Helicobacter pylori -Associated Gastritis

Abstract

ABSTRACT Colonization of the gastric mucosa with Helicobacter pylori is associated with a dense infiltration of granulocytes into the lamina propria in the active phase of gastritis. In this study, we investigated the involvement of epithelial cell-derived neutrophil-activating protein 78 (ENA-78) in development of H. pylori -associated gastritis. Antral biopsies from 27 patients with H. pylori -associated gastritis and 25 from H. pylori -negative individuals were first analyzed for ENA-78 and interleukin-8 (IL-8) mRNA by semiquantitative reverse transcription (RT)-PCR. In H. pylori -positive patients, significantly elevated levels were found for both chemokines ( P < 0.05). Only IL-8 mRNA levels differed significantly ( P < 0.05) in H. pylori -infected individuals who had serum antibodies for cytotoxin-associated protein CagA versus H. pylori -infected CagA-negative persons. Quantification of ENA-78 transcript levels by competitive RT-PCR yielded a significant 45-fold upregulation for ENA-78 transcripts in biopsies of H. pylori -positive versus H. pylori -negative patients ( P < 0.05). In contrast to earlier findings with IL-8, the degree of ENA-78 mRNA upregulation was independent of the grade of activity of gastritis. Immunofluorescence studies on tissues of antral biopsies localized ENA-78 protein expression mainly to the gastric epithelium of H. pylori -positive patients, while control tissues were negative. Upregulation of ENA-78 and IL-8 mRNA and protein expression was also observed in an in vitro system using a gastric adenocarcinoma cell line. Only viable H. pylori yielded a strong ENA-78 and IL-8 induction, while H. pylori outer membrane proteins or water-soluble proteins had no significant effect. These data provide evidence for the importance of both IL-8 and ENA-78 in the development and perpetuation of H. pylori -associated gastritis.