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

Masaaki Shimada, Takafumi Ando, Richard M. Peek, Osamu Watanabe, Kazuhiro Ishiguro, Osamu Maeda, Daisuke Ishikawa, Motofusa Hasegawa, Kenji Ina, Naoki Ohmiya, Yasumasa Niwa, Hidemi Goto

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1144-1150
Number of pages7
JournalEuropean Journal of Gastroenterology and Hepatology
Volume20
Issue number12
DOIs
Publication statusPublished - 01-12-2008
Externally publishedYes

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Interleukin-18
Helicobacter Infections
Helicobacter pylori
Stomach
Up-Regulation
Epithelial Cells
Dyspepsia
Stomach Ulcer
Interleukin-1
Caspase 3
Ulcer
Fas Ligand Protein
Stomach Neoplasms
Enzymes
Western Blotting
Pyloric Antrum
Cell Line
Wounds and Injuries
Endoscopy
Mucous Membrane

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Shimada, Masaaki ; Ando, Takafumi ; Peek, Richard M. ; Watanabe, Osamu ; Ishiguro, Kazuhiro ; Maeda, Osamu ; Ishikawa, Daisuke ; Hasegawa, Motofusa ; Ina, Kenji ; Ohmiya, Naoki ; Niwa, Yasumasa ; Goto, Hidemi. / Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells. In: European Journal of Gastroenterology and Hepatology. 2008 ; Vol. 20, No. 12. pp. 1144-1150.
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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.",
author = "Masaaki Shimada and Takafumi Ando and Peek, {Richard M.} and Osamu Watanabe and Kazuhiro Ishiguro and Osamu Maeda and Daisuke Ishikawa and Motofusa Hasegawa and Kenji Ina and Naoki Ohmiya and Yasumasa Niwa and Hidemi Goto",
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Shimada, M, Ando, T, Peek, RM, Watanabe, O, Ishiguro, K, Maeda, O, Ishikawa, D, Hasegawa, M, Ina, K, Ohmiya, N, Niwa, Y & Goto, H 2008, 'Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells', European Journal of Gastroenterology and Hepatology, vol. 20, no. 12, pp. 1144-1150. https://doi.org/10.1097/MEG.0b013e32830edb15

Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells. / Shimada, Masaaki; Ando, Takafumi; Peek, Richard M.; Watanabe, Osamu; Ishiguro, Kazuhiro; Maeda, Osamu; Ishikawa, Daisuke; Hasegawa, Motofusa; Ina, Kenji; Ohmiya, Naoki; Niwa, Yasumasa; Goto, Hidemi.

In: European Journal of Gastroenterology and Hepatology, Vol. 20, No. 12, 01.12.2008, p. 1144-1150.

Research output: Contribution to journalArticle

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 - 2008/12/1

Y1 - 2008/12/1

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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