| RRC ID |
18108
|
| Author |
Tu SP, Quante M, Bhagat G, Takaishi S, Cui G, Yang XD, Muthuplani S, Shibata W, Fox JG, Pritchard DM, Wang TC.
|
| Title |
IFN-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis.
|
| Journal |
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.
|
| Volume |
71(12)
|
| Pages |
4247-59
|
| Published |
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
|
| Times Cited |
68
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
MKN28(RCB1000) |
