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Helicobacter pylori Activates IL‐6‐STAT3 Signaling in Human Gastric Cancer Cells: Potential Roles for Reactive Oxygen Species
Author(s) -
Piao JuanYu,
Lee Hee Geum,
Kim SuJung,
Kim DoHee,
Han Hyeongjun,
Ngo HoangKieuChi,
Park SinAye,
Woo JeongHwa,
Lee JeongSang,
Na HyeKyung,
Cha YoungNam,
Surh YoungJoon
Publication year - 2016
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/hel.12298
Subject(s) - stat3 , stat protein , helicobacter pylori , microbiology and biotechnology , electrophoretic mobility shift assay , signal transduction , chemistry , western blot , downregulation and upregulation , transcription factor , reactive oxygen species , biology , cancer research , biochemistry , gene , genetics
Background Recent 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 Methods AGS 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. Results H. 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. Conclusions H. 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.