Human gastric epithelium produces IL-4 and IL-4delta2 isoform only upon Helicobacter pylori infection

Abstract

Recent evidence suggests that interleukin-4 (IL-4) is related to mucosal tolerance by which an injurious immune response is prevented, suppressed or shifted to a non-injurious response. We investigated the expression of IL-4 and its splice variant isoform IL-4delta2 in gastric epithelial cells of healthy subjects and gastritis patients infected with Helicobacter pylori (H. pylori) with or without the cag pathogenicity island (cag-PAI). IL-4 and IL-4delta2 mRNAs were evaluated in microdissected gastric epithelium and in AGS cell lines co-cultured with H. pylori B128 or SS1 strains. IL-4 mRNA was consistently detected in microdissected gastric epithelial cells from healthy subjects. The IL-4 mRNA expression was low in H. pylori?infected patients, and markedly reduced in cag-PAI-positive ones. IL-4delta2 mRNA was expressed on gastric epithelium of H. pylori-infected patients, but not in healthy subjects. The IL-4delta2 expression was lower in cag-PAI-positive than in cag-PAI-negative H. pylori infected patients. AGS cells also produced IL-4 mRNA upon SS1 strain stimulation, whereas IL-4delta2 mRNA expression was detected in AGS co-cultured with either SS1 or B128 strains. An inverse correlation was documented between IL-4 and IL-4delta2 mRNA expression by microdissected gastric epithelial cells and the score of gastritis. IL-4, but not IL-4delta2, is expressed by gastric epithelium of healthy subjects, whereas IL-4delta2 and lesser IL-4 mRNA are detectable in the gastric epithelium of H. pylori-infected patients. Data suggest that gastric epithelial cells might regulate the balance between tolerance and immune response by the fine tuning of IL-4 and IL-4delta2 expression.