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Helicobacter pylori Activates IL-6-STAT3 Signaling in Human Gastric Cancer Cells: Potential Roles for Reactive Oxygen Species

Cited 25 time in Web of Science Cited 29 time in Scopus
Authors
Piao, Juan-Yu; Lee, Hee Geum; Kim, Su-Jung; Kim, Do-Hee; Han, Hyeong-jun; Ngo, Hoang-Kieu-Chi; Park, Sin-Aye; Woo, Jeong-Hwa; Lee, Jeong-Sang; Na, Hye-Kyung; Cha, Young-Nam; Surh, Young-Joon
Issue Date
2016-10
Citation
Helicobacter, Vol.21 No.5, pp.405-416
Keywords
Helicobacter pylorigastritissignal transducer and activator of transcription 3reactive oxygen speciesinterleukin-6interleukin-6 receptor
Abstract
BackgroundRecent studies have shown that Helicobacter pylori (H. pylori) activates signal transducer and activator of transcription 3 (STAT3) that plays an important role in gastric carcinogenesis. However, the molecular mechanism underlying H. pylori-mediated STAT3 activation is still not fully understood. In this study, we investigated H. pylori-induced activation of STAT3 signaling in AGS human gastric cancer cells and the underlying mechanism. Materials and MethodsAGS cells were cocultured with H. pylori, and STAT3 activation was assessed by Western blot analysis, electrophoretic mobility shift assay and immunocytochemistry. To demonstrate the involvement of reactive oxygen species (ROS) in H. pylori-activated STAT3 signaling, the antioxidant N-acetylcysteine was utilized. The expression and production of interleukin-6 (IL-6) were measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The interaction between IL-6 and IL-6 receptor (IL-6R) was determined by the immunoprecipitation assay. ResultsH. pylori activates STAT3 as evidenced by increases in phosphorylation on Tyr(705), nuclear localization, DNA binding and transcriptional activity of this transcription factor. The nuclear translocation of STAT3 was also observed in H. pylori-inoculated mouse stomach. In the subsequent study, we found that H. pylori-induced STAT3 phosphorylation was dependent on IL-6. Notably, the increased IL-6 expression and the IL-6 and IL-6R binding were mediated by ROS produced as a consequence of H. pylori infection. ConclusionsH. pylori-induced STAT3 activation is mediated, at least in part, through ROS-induced upregulation of IL-6 expression. These findings provide a novel molecular mechanism responsible for H. pylori-induced gastritis and gastric carcinogenesis.
ISSN
1083-4389
URI
https://hdl.handle.net/10371/172767
DOI
https://doi.org/10.1111/hel.12298
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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