TY - JOUR
T1 - Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells
AU - Shimada, Masaaki
AU - Ando, Takafumi
AU - Peek, Richard M.
AU - Watanabe, Osamu
AU - Ishiguro, Kazuhiro
AU - Maeda, Osamu
AU - Ishikawa, Daisuke
AU - Hasegawa, Motofusa
AU - Ina, Kenji
AU - Ohmiya, Naoki
AU - Niwa, Yasumasa
AU - Goto, Hidemi
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
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U2 - 10.1097/MEG.0b013e32830edb15
DO - 10.1097/MEG.0b013e32830edb15
M3 - Article
C2 - 18946358
AN - SCOPUS:56749150588
SN - 0954-691X
VL - 20
SP - 1144
EP - 1150
JO - European Journal of Gastroenterology and Hepatology
JF - European Journal of Gastroenterology and Hepatology
IS - 12
ER -
