title: Involvement of Ras and AP-1 in Helicobacter pylori-induced expression of COX-2 and iNOS in gastric epithelial AGS cells.
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.
authors.affiliation: Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Seoul, 120-752, Korea.
authors.forename: Soon Ok
authors.initials: SO
authors.lastname: Cho
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000378:metabolism; D004790:Enzyme Induction / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005753:Gastric Mucosa / Q000378:metabolism / Q000821:virology; D005756:Gastritis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation / Q000235:genetics; D016481:Helicobacter Infections / Q000235:genetics* / Q000821:virology; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D009573:Nitrites / Q000378:metabolism; D010437:Peptic Ulcer / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014162:Transfection; D018631:ras Proteins / Q000502:physiology*
chemical_list: D009573:Nitrites; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D018631:ras Proteins; D015232:Dinoprostone