Comparison of CXC chemokines ENA-78 and interleukin-8 expression in Helicobacter pylori-associated gastritis

Colonization of the gastric mucosa with Helicobacter pylori is associated w ith a dense infiltration of granulocytes into the lamina propria in the act ive phase of gastritis. In this study, we investigated the involvement of e pithelial cell-derived neutrophil-activating protein 78 (ENA-78) in develop ment of H. pylori-associated gastritis. Antral biopsies from 27 patients wi th H. pylori-associated gastritis and 25 from H. pylori-negative individual s were first analyzed for ENA-78 and interleukin-8 (IL-8) mRNA by semiquant itative reverse transcription (RT)-PCR In H. pylori-positive patients, sign ificantly elevated levels were found for both chemokines (P < 0.05). Only I L-8 mRNA levels differed significantly (P < 0.05) in H. pylori-infected ind ividuals who had serum antibodies for cytotoxin-associated protein CagA ver sus H. pylori-infected CagA-negative persons. Quantification of ENA-78 tran script levels by competitive RT-PCR yielded a significant 45-fold upregulat ion for ENA-78 transcripts in biopsies of H. pylori-positive versus H. pylo ri-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 act ivity of gastritis. Immunofluorescence studies on tissues of antral biopsie s localized ENA-78 protein expression mainly to the gastric epithelium of H . pylori-positive patients, while control tissues were negative. Upregulati on of ENA-78 and IL-8 mRNA and protein expression was also observed in an i n vitro system using a gastric adenocarcinoma cell line. Only viable H. pyl ori yielded a strong ENA-rs and IL-8 induction, while H. pylori outer membr ane proteins or water-soluble proteins had no significant effect. These dat a provide evidence for the importance of both IL-8 and ENA-78 in the develo pment and perpetuation of H. pylori-associated gastritis.