Signaling for integrin alpha5/beta1 expression in Helicobacter pylori-infected gastric epithelial AGS cells.
Integrin expression in cancer tissues demonstrates its possible contribution to tumor progression, invasion, and metastasis. Helicobacter pylori (H. pylori) infection is related to gastric cancer and gastric inflammation. H. pylori induced upregulation in expression of integrin in gastric epithelia cells. Reactive oxygen species (ROS) are considered as an important regulator in the pathogenesis of H. pylori-induced gastric ulceration and carcinogenesis. Integrin expression may be regulated by oxidant-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of integrin alpha5 and integrin beta1, and whether H. pylori-induced expression of integrin alpha5 and integrin beta1 are inhibited in the cells transfected with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IkappaBalpha(MAD-3) or treated with DPI, an inhibitor of NADPH oxidase. As a result, H. pylori induced the expression of integrin alpha5 and integrin beta1 in gastric adenocarcinoma (AGS) cells time-dependently. Treatment of DPI or transfection with mutant genes for Ras (ras N-17), c-jun (TAM67), and IkappaBalpha(MAD3) inhibited H. pylori-induced expression of integrin alpha5 and integrin beta1 in AGS cells. In conclusion, H. pylori activates Ras, NF-kappaB, and AP-1 and thus induces the expression of integrin alpha5 and integrin beta1 in gastric epithelial cells. Inhibition of ROS production by DPI suppressed the expression of integrin alpha5 and integrin beta1 in gastric epithelial cells. The results suggest the possible involvement of NADPH oxidase for ROS production in H. pylori-infected gastric epithelial cells.
Cho
Soon Ok
SO
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-749, Korea.
Kim
Kyung Hwan
KH
Yoon
Joo-Heon
JH
Kim
Hyeyoung
H
D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D015398:Signal Transduction; D013270:Stomach / Q000166:cytology / Q000382:microbiology
D039081:Integrin alpha5beta1