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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.

 Seong Bok Jang  ;  Yoon Jung Lee  ;  Lay Ahyoung Lim  ;  Kyung-Mi Park  ;  Bong-Ju Kwon  ;  Jong Soo Woo  ;  Yong-IL Kim  ;  Min Soo Park  ;  Kyung Hwan Kim  ;  Kyungsoo Park 
 DIGESTIVE DISEASES AND SCIENCES, Vol.55(4) : 988-996, 2010 
Journal Title
Issue Date
Adenocarcinoma/genetics* ; Adenocarcinoma/pathology ; Adenocarcinoma/virology ; Cell Line, Tumor ; Cyclooxygenase 2/genetics* ; Dinoprostone/metabolism ; Enzyme Induction/genetics ; Epithelial Cells/metabolism ; Epithelial Cells/virology ; Gastric Mucosa/metabolism ; Gastric Mucosa/virology ; Gastritis/genetics* ; Gastritis/pathology ; Gastritis/virology ; Gene Expression Regulation/genetics ; Helicobacter Infections/genetics* ; Helicobacter Infections/virology ; Helicobacter pylori/genetics* ; Humans ; Nitric Oxide Synthase Type II/genetics* ; Nitrites/metabolism ; Peptic Ulcer/genetics* ; Peptic Ulcer/pathology* ; Peptic Ulcer/virology ; Proto-Oncogene Proteins c-fos/genetics* ; Proto-Oncogene Proteins c-jun/genetics* ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/pathology ; Stomach Neoplasms/virology ; Transcription Factor AP-1/physiology* ; Transfection ; ras Proteins/physiology
AP-1 ; Gastric epithelial cells ; Helicobacter pylori ; c-Fos ; c-Jun ; RAS
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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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
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