Effects of nonsteroidal anti-inflammatory drugs on Helicobacter pylori-infected gastric mucosae of mice: Apoptosis, cell proliferation, and inflammatory activity

Il Kim Tae Il Kim, Chan Lee Yong Chan Lee, Hyoung Lee Kwang Hyoung Lee, Ho Han Jae Ho Han, Yoon Chon Chae Yoon Chon, Myoung Moon Young Myoung Moon, Kyung Kang Jin Kyung Kang, Suh Park In Suh Park

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Abstract

Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are two well-known important causative factors of gastric damage. While H. pylori increases apoptosis and the proliferation of gastric epithelial cells and is an important factor in peptic ulcer and gastric cancer, NSAIDs induce cell apoptosis and have antineoplastic effects. We investigated the effects of NSAIDs (a nonselective cyclooxygenase [COX] inhibitor [indomethacin] and a selective COX-2 inhibitor [NS-398]) on the apoptosis and proliferation of gastric epithelial cells and gastric inflammation in H. pylori-infected mice. C57BL/6 mice were sacrificed 8 weeks after H. pylori SS1 inoculation. Indomethacin (2 mg/kg) or NS-398 (10 mg/kg) was administered subcutaneously once daily for 10 days before sacrifice. The following were assessed: gastric inflammatory activity, gastric COX protein expression by Western blotting; gastric prostaglandin E2 levels by enzyme immunoassay, apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and cell proliferation by Ki67 immunostaining. Compared to the controls, H. pylori infection and/or NSAID treatment increased COX-1 and COX-2 protein expression. Gastric prostaglandin E2 levels, apoptotic index, cell proliferation index, neutrophil activity, and the degree of chronic inflammation were all increased by H. pylori infection, and these effects were significantly decreased by indomethacin treatment. However, NS-398 treatment after H. pylori infection did not induce a significant reduction, although it did result in a tendency to decrease. These results show that NSAIDs can reverse the increased apoptosis and proliferation of epithelial cells and inflammatory activity in the stomachs of H. pylori-infected mice and that, like COX-2 activation, COX-1 induction contributes to the change of gastric mucosal cell turnover and inflammation induced by H. pylori infection.

Original languageEnglish
Pages (from-to)5056-5063
Number of pages8
JournalInfection and Immunity
Volume69
Issue number8
DOIs
Publication statusPublished - 2001 Aug 4

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All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Tae Il Kim, I. K., Yong Chan Lee, C. L., Kwang Hyoung Lee, H. L., Jae Ho Han, H. H., Chae Yoon Chon, Y. C., Young Myoung Moon, M. M., Jin Kyung Kang, K. K., & In Suh Park, S. P. (2001). Effects of nonsteroidal anti-inflammatory drugs on Helicobacter pylori-infected gastric mucosae of mice: Apoptosis, cell proliferation, and inflammatory activity. Infection and Immunity, 69(8), 5056-5063. https://doi.org/10.1128/IAI.69.8.5056-5063.2001