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|a Tu, Shui Ping
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|a Massachusetts Institute of Technology. Department of Biological Engineering
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|a Massachusetts Institute of Technology. Division of Comparative Medicine
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|a Muthupalani, Sureshkumar
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|a Fox, James G.
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|a Quante, Michael
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|a Bhagat, Govind
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|a Takaishi, Shigeo
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|a Cui, Guanglin
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|a Yang, Xiang Dong
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|a Muthupalani, Sureshkumar
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|a Shibata, Wataru
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|a Fox, James G.
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|a Pritchard, D. Mark
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|a Wang, Timothy C.
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|a Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis
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|b American Association for Cancer Research,
|c 2012-12-12T20:53:28Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/75438
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|a Author Manuscript 2012 June 15.
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|a 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[superscript +]/K[superscript +]-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[superscript +] 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. Cancer Res; 71(12); 4247-59.
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|t Cancer Research
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