論文 - 詳細
| RRC ID | 18108 |
|---|---|
| 著者 | Tu SP, Quante M, Bhagat G, Takaishi S, Cui G, Yang XD, Muthuplani S, Shibata W, Fox JG, Pritchard DM, Wang TC. |
| タイトル | IFN-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis. |
| ジャーナル | Cancer Res |
| Abstract |
IFN-γ mediates responses to bacterial infection and autoimmune disease, but it is also an important tumor suppressor. It is upregulated in the gastric mucosa by chronic Helicobacter infection; however, whether it plays a positive or negative role in inflammation-associated gastric carcinogenesis is unexplored. To study this question, we generated an H(+)/K(+)-ATPase-IFN-γ transgenic mouse that overexpresses murine IFN-γ in the stomach mucosa. In contrast to the expected proinflammatory role during infection, we found that IFN-γ overexpression failed to induce gastritis and instead inhibited gastric carcinogenesis induced by interleukin-1beta (IL-1β) and/or Helicobacter infection. Helper T cell (Th) 1 and Th17 immune responses were inhibited by IFN-γ through Fas induction and apoptosis in CD4 T cells. IFN-γ also induced autophagy in gastric epithelial cells through increased expression of Beclin-1. Finally, in the gastric epithelium, IFN-γ also inhibited IL-1β- and Helicobacter-induced epithelial apoptosis, proliferation, and Dckl1(+) cell expansion. Taken together, our results suggest that IFN-γ coordinately inhibits bacterial infection and carcinogenesis in the gastric mucosa by suppressing putative gastric progenitor cell expansion and reducing epithelial cell apoptosis via induction of an autophagic program. |
| 巻・号 | 71(12) |
| ページ | 4247-59 |
| 公開日 | 2011-6-15 |
| DOI | 10.1158/0008-5472.CAN-10-4009 |
| PII | 0008-5472.CAN-10-4009 |
| PMID | 21512143 |
| PMC | PMC3139967 |
| MeSH | Animals Apoptosis* Apoptosis Regulatory Proteins / physiology Autophagy* Beclin-1 Cell Line, Tumor Cell Proliferation Doublecortin-Like Kinases Gastric Mucosa / pathology Gastritis / etiology H(+)-K(+)-Exchanging ATPase / physiology Helicobacter Infections / complications* Humans Interferon-gamma / physiology* Interleukin-1beta / physiology Metaplasia Mice Protein Serine-Threonine Kinases / analysis Stomach Neoplasms / etiology Stomach Neoplasms / pathology Stomach Neoplasms / prevention & control* T-Lymphocytes / physiology* Th17 Cells / immunology |
| IF | 9.727 |
| 引用数 | 68 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN28(RCB1000) |