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

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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.

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Acknowledgments

This study was supported by a grant of the Korea Health 21 R&D Project, the Ministry of Health&Welfare, Republic of Korea (A080975), and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R11-2007-040-01002-0) (to H. Kim). H. Kim is grateful to Brain Korea 21 Project, College of Human Ecology, Yonsei University.

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  1. Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Seoul, 120-752, Korea

    Soon Ok Cho & Kyung Hwan Kim

  2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, 120-752, Korea

    Joo Weon Lim

  3. Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seoul, 120-749, Korea

    Hyeyoung Kim

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  1. Soon Ok Cho
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Cho, S.O., Lim, J.W., Kim, K.H. et al. Involvement of Ras and AP-1 in Helicobacter pylori-Induced Expression of COX-2 and iNOS in Gastric Epithelial AGS Cells. Dig Dis Sci 55, 988–996 (2010). https://doi.org/10.1007/s10620-009-0828-y

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