title: Interaction of omeprazole and Helicobacter pylori-induced nuclear factor-κB activation and mediators in gastric epithelial cells.
abstract: BACKGROUND
  Omeprazole (OMP), a proton pump inhibitor, is a highly effective drug for the management of acid-related disorders. Infections resulting from cytotoxin antigen A (CagA) positive Helicobacter pylori strains have been associated with higher grades of gastric mucosal inflammation. Nuclear factor (NF)-κB activation has been reported to participate in H. pylori-induced gastritis in humans. The complex interaction of OMP on the H. pylori and NF-κB related molecular mechanisms within the gastric mucosa remains unclear. In the present study, we investigated OMP, specifically its effects on NF-κB activation, and COX-2, IL-6, and IL-8 production in gastric cells (Kato-III cells) treated with CagA positive (CagA(+)) and negative (CagA(-)) H. pylori strains.
  
  
  METHODS
  Kato-III cells were stimulated with H. pylori water extracts (HPE) containing ATCC 43504 (CagA(+)) and ATCC 51932 (CagA(-)) strains. NF-κB activation, inhibitory IκB expression and phosphorylation, and cyclooxygenase (COX)-2, interleukin (IL)-6, and IL-8 expression were assessed in the absence and presence of OMP.
  
  
  RESULTS
  Both CagA(+) and CagA(-) HPE induced NF-κB activation, whereas OMP suppressed NF-κB activation in the CagA(-) strain. HPE demonstrated a similar effect on IκB protein expression in the absence and presence of OMP. OMP alone decreased IκB phosphorylation without promoting NF-κB and IκB expression. Additionally, both CagA(+) and CagA(-) HPE induced COX-2 expression, but no significant effect on IL-6 and IL-8. However, OMP downregulated the transcription of COX-2, IL-6, and IL-8 in CagA(-) HPE treated cells.
  
  
  CONCLUSIONS
  Using the Kato-III cells model, H. pylori induces NF-κB activation in a CagA-independent manner. Both CagA(+) HPE and CagA(-) HPE induced COX-2 gene expression, but not for IL-6 and IL-8 expression. However, OMP suppressed NF-κB activation via a downregulation of IκB phosphorylation in CagA(-) HPE treated condition. OMP also suppressed CagA(-)H. pylori induced-transcription of proinflammatory COX-2, IL-6, and IL-8. OMP may provide different effects on CagA(+) and CagA(-)H. pylori infection conditions.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Peng
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, ROC.
authors.forename: Lan-Ru
authors.initials: LR
authors.lastname: Huang
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC.
authors.forename: Ching-Lin
authors.initials: CL
authors.lastname: Shyu
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Ching-Chang
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC. Electronic address: spho@nchu.edu.tw.
authors.forename: Shu-Peng
authors.initials: SP
authors.lastname: Ho
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D016480:Helicobacter pylori / Q000502:physiology*; D016328:NF-kappa B / Q000187:drug effects*; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D054328:Proton Pump Inhibitors; D009853:Omeprazole
keywords: Helicobacter pylori; cytotoxin antigen A; interleukin-6; interleukin-8; nuclear factor-κB activation; omeprazole