Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells

Abstract

Background Helicobacter pylori infection induces a biased T helper type 1 (Th1) response that produces IFN-γ and Fas ligand (FasL). Th1 cytokines are associated with apoptosis in the gastric epithelial cells. Aim We aimed to define the role of the recently cloned IL-18, a IFN-γ inducing factor, in gastric mucosal injury induced by H. pylori infection. Methods Twenty-seven gastric ulcer (GU) patients and 20 functional dyspepsia (FD) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used for histological examination, H. pylori culture and in-situ stimulation for 48 h in the presence of 10 µg/ml phytohemagglutinin-P. IL-18, IFN-γ, and soluble FasL (sFasL) levels in culture supernatants were assayed by the enzyme-linked immunosorbent assay method. IL-18, IL-1β-converting enzyme (ICE) and caspase-3 were evaluated by western blotting in gastric cancer cell lines (MKN45) cocultured with H. pylori. Results All 27 GU patients and ten out of 20 FD patients were found to be H. pylori-positive, whereas ten FD patients were H. pylori-negative. Antral mucosal tissues from H. pylori-positive FD patients contained (P < 0.01) higher levels of IL-18, IFN-γ, and sFasL than those from uninfected FD patients. IL-18, IFN-γ, and sFasL levels at the ulcer site were significantly (P < 0.01) higher than those at distant sites in the antrum. A significant relationship was seen between IL-18 and IFN-γ levels at the ulcer site (r = 0.7, P < 0.01). H. pylori eradication led to a significant decrease in the levels of IL-18, IFN-γ, and sFasL at the ulcer site. Western blotting showed that IL-18, ICE, and caspase-3 were activated in gastric cancer cell lines cocultured with H. pylori. Conclusion This study suggests that H. pylori infection enhanced mucosal injury by stimulating a Th1 response, which was mediated by IL-18 upregulation as well as activation of ICE and caspase-3.

Pattern-Recognition Receptors and Gastric Cancer

“…Later, Hitzler et al (240) showed in both cultured DCs and in vivo that H. pylori infection activates caspase-1, leading to IL-1β/IL-18 processing and secretion. Consistently, three studies, using human GC cell lines, gastric tissue, and murine models, confirmed increased expression of caspase-1, IL-1β, and IL-18 in H. pylori -infected cells (171, 241, 242). Further, Jiang et al (243), also using a murine model, have reported the expression of NLRP3 inflammasome-related molecules as well as serum IL-1β, IL-18, and IL-33 levels to be significantly increased in H. pylori -infected mice.…”

CagA-Dependent Downregulation of B7-H2 Expression on Gastric Mucosa and Inhibition of Th17 Responses during Helicobacter pylori Infection

“…IFNγ is produced within the H. pylori infected gastric mucosa (40), and previously we showed a synergistic effect of IFNγ and H. pylori on B7-H1 upregulation on GEC (18). Thus, we examined whether IFNγ could modulate H. pylori -mediated B7-H2 downregulation on GECs.…”

Helicobacter Pylori Promote B7-H1 Expression by Suppressing miR-152 and miR-200b in Gastric Cancer Cells

“…We found a marked increase in B7-H1 expression on the surface of the AGS cells 24 h after infection with an HP strain (Fig 2). Because interferon-γ (IFN-γ) can be produced within the HP-infected gastric mucosa [23], which might also stimulate B7-H1 expression [24], we investigated whether IFN-γ could modulate HP-mediated B7-H1 expression in AGS cells. We found that the IFN-γ treatment also markedly stimulated B7-H1 expression in AGS cells (Fig 2).…”