Interaction of omeprazole and Helicobacter pylori-induced nuclear factor-κB activation and mediators in gastric epithelial cells

Yen-Chun Peng; Lan-Ru Huang; Ching-Lin Shyu; Ching-Chang Cheng; Shu-Peng Ho

doi:10.1016/j.jcma.2014.07.006

Interaction of omeprazole and Helicobacter pylori-induced nuclear factor-κB activation and mediators in gastric epithelial cells

J Chin Med Assoc. 2014 Nov;77(11):567-72. doi: 10.1016/j.jcma.2014.07.006. Epub 2014 Sep 7.

Authors

Yen-Chun Peng¹, Lan-Ru Huang², Ching-Lin Shyu³, Ching-Chang Cheng⁴, Shu-Peng Ho⁵

Affiliations

¹ 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.
² Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, ROC.
³ Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC.
⁴ Department of Nutrition, China Medical University, Taichung, Taiwan, ROC.
⁵ Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC. Electronic address: spho@nchu.edu.tw.

PMID: 25205289
DOI: 10.1016/j.jcma.2014.07.006

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.

Conclusion: 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.

Keywords: Helicobacter pylori; cytotoxin antigen A; interleukin-6; interleukin-8; nuclear factor-κB activation; omeprazole.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cells, Cultured
Epithelial Cells / drug effects*
Epithelial Cells / metabolism
Gastric Mucosa / drug effects
Helicobacter pylori / physiology*
NF-kappa B / drug effects*
Omeprazole / pharmacology*
Proton Pump Inhibitors / pharmacology*

Substances

NF-kappa B
Proton Pump Inhibitors
Omeprazole