Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis
Author Manuscript 2012 June 15.
| Main Authors: | , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for Cancer Research
2012
|
| Online Access: | http://hdl.handle.net/1721.1/75438 https://orcid.org/0000-0001-9307-6116 |
| _version_ | 1811084089022742528 |
|---|---|
| author | Tu, Shui Ping Quante, Michael Bhagat, Govind Takaishi, Shigeo Cui, Guanglin Yang, Xiang Dong Muthupalani, Sureshkumar Shibata, Wataru Fox, James G. Pritchard, D. Mark Wang, Timothy C. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Tu, Shui Ping Quante, Michael Bhagat, Govind Takaishi, Shigeo Cui, Guanglin Yang, Xiang Dong Muthupalani, Sureshkumar Shibata, Wataru Fox, James G. Pritchard, D. Mark Wang, Timothy C. |
| author_sort | Tu, Shui Ping |
| collection | MIT |
| description | Author Manuscript 2012 June 15. |
| first_indexed | 2024-09-23T12:44:34Z |
| format | Article |
| id | mit-1721.1/75438 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:44:34Z |
| publishDate | 2012 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/754382022-10-01T10:50:35Z Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis Tu, Shui Ping Quante, Michael Bhagat, Govind Takaishi, Shigeo Cui, Guanglin Yang, Xiang Dong Muthupalani, Sureshkumar Shibata, Wataru Fox, James G. Pritchard, D. Mark Wang, Timothy C. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Muthupalani, Sureshkumar Fox, James G. Author Manuscript 2012 June 15. 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. 2012-12-12T20:53:28Z 2012-12-12T20:53:28Z 2011-04 2011-04 Article http://purl.org/eprint/type/JournalArticle 0008-5472 1538-7445 http://hdl.handle.net/1721.1/75438 Tu, S. P. et al. “IFN- Inhibits Gastric Carcinogenesis by Inducing Epithelial Cell Autophagy and T-Cell Apoptosis.” Cancer Research 71.12 (2011): 4247–4259. https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1158/0008-5472.CAN-10-4009 Cancer Research Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | Tu, Shui Ping Quante, Michael Bhagat, Govind Takaishi, Shigeo Cui, Guanglin Yang, Xiang Dong Muthupalani, Sureshkumar Shibata, Wataru Fox, James G. Pritchard, D. Mark Wang, Timothy C. Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis |
| title | Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis |
| title_full | Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis |
| title_fullStr | Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis |
| title_full_unstemmed | Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis |
| title_short | Interferon-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T cell apoptosis |
| title_sort | interferon γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and t cell apoptosis |
| url | http://hdl.handle.net/1721.1/75438 https://orcid.org/0000-0001-9307-6116 |
| work_keys_str_mv | AT tushuiping interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT quantemichael interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT bhagatgovind interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT takaishishigeo interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT cuiguanglin interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT yangxiangdong interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT muthupalanisureshkumar interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT shibatawataru interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT foxjamesg interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT pritcharddmark interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis AT wangtimothyc interferonginhibitsgastriccarcinogenesisbyinducingepithelialcellautophagyandtcellapoptosis |