Digestive Diseases and Sciences

, Volume 55, Issue 4, pp 988–996

Involvement of Ras and AP-1 in Helicobacter pylori-Induced Expression of COX-2 and iNOS in Gastric Epithelial AGS Cells

  • Soon Ok Cho
  • Joo Weon Lim
  • Kyung Hwan Kim
  • Hyeyoung Kim
Original Article

DOI: 10.1007/s10620-009-0828-y

Cite this article as:
Cho, S.O., Lim, J.W., Kim, K.H. et al. Dig Dis Sci (2010) 55: 988. doi:10.1007/s10620-009-0828-y

Abstract

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. The genetic differences of H. pylori isolates play a role in the clinical outcome of the infection. Inflammatory genes including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in H. pylori gastritis. Transcription factor AP-1 is composed of c-Fos and c-Jun and mediates inflammation and carcinogenesis. Ras acts as a regulator for AP-1 activation in various cells. We investigated whether H. pylori in a Korean isolate (HP99), a cagA+, vacA+ strain, induces the expression of c-Fos and c-Jun for AP-1 activation to induce COX-2 and iNOS and whether HP99-induced expressions of COX-2 and iNOS are mediated by Ras and AP-1, determined by the expressions of c-Fos and c-Jun, in gastric epithelial AGS cells, using transfection with mutant genes for Ras (ras N-17) and c-Jun (TAM-67). As a result, HP99 induced the expression of c-Fos and c-Jun and the expressions of COX-2 and iNOS in AGS cells. Transfection with mutant genes for Ras or c-Jun suppressed HP99-induced expressions of COX-2 and iNOS in AGS cells. In conclusion, H. pylori in a Korean isolate induces the expression of COX-2 and iNOS via AP-1 activation, which may be mediated by Ras and the expression of c-Fos and c-Jun in gastric epithelial cells.

Keywords

AP-1Gastric epithelial cellsHelicobacter pyloric-Fosc-JunRAS

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Soon Ok Cho
    • 1
  • Joo Weon Lim
    • 2
  • Kyung Hwan Kim
    • 1
  • Hyeyoung Kim
    • 3
  1. 1.Department of PharmacologyBrain Korea 21 Project for Medical SciencesSeoulKorea
  2. 2.Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
  3. 3.Department of Food and Nutrition, Brain Korea 21 ProjectYonsei University College of Human EcologySeoulKorea