Down-regulation of epithelial IL-8 responses in Helicobacter pylori-infected duodenal ulcer patients depends on host factors, rather than bacterial factors

• Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide. Although the majority of the infected individuals remain asymptomatic carriers of the bacteria, approximately 15% develop peptic ulcers, which are most prevalent in the duodenum. H. pylori induce a vigorous immune response which, however, fails to clear the infection. Instead, the chronic inflammation that arises in the infected gastroduodenal mucosa may be involved in the development of H. pylori-associated peptic ulcers. We have previously shown that duodenal ulcer (DU) patients have a significantly lower epithelial cytokine, e.g. IL-8, response in the duodenum than asymptomatic (AS) carriers. In this study we have further investigated the mechanisms behind this finding, i.e. whether it can be explained by bacterial factors, down-regulation of epithelial cytokine production by regulatory T cells, or an impaired ability of the duodenal epithelium in DU patients to produce cytokines. Gastric AGS, and intestinal T84 epithelial cell lines were stimulated with H. pylori strains isolated from DU patients and AS carriers, respectively. All strains were found to induce comparable cytokine and cytokine receptor expression in epithelial cells. Regulatory T cells (CD4+ CD25(high)), isolated from human peripheral blood and cocultured with H. pylori stimulated AGS cells, were found to slightly suppress H. pylori-induced epithelial cytokine production. Furthermore, primary cultures of duodenal epithelial cells from DU patients were found to produce markedly lower amounts of cytokines than epithelial cells isolated from AS carriers. These results suggest that the lower epithelial cytokine responses in the duodenum of DU patients, which may be of importance for the pathogenesis of H. pylori-induced duodenal ulcers, most likely can be explained by host factors, i.e. mainly a decreased ability of the duodenal epithelium to produce cytokines, but possibly partly also down-regulation by regulatory T cells.

Keyword

CD4-Positive T-Lymphocytes/immunology

Cell Line

Coculture Techniques/methods

Down-Regulation/immunology

Duodenal Ulcer/immunology/*microbiology

Epithelial Cells/immunology

Helicobacter Infections/*immunology

Helicobacter pylori/*immunology

Humans

Interleukin-8/*immunology

Intestinal Mucosa/immunology

Receptors

Cytokine/immunology

Receptors

Interleukin-2/immunology

T-Lymphocytes/immunology

Transforming Growth Factor beta/immunology

Publication and Content Type

ref (subject category)

art (subject category)