Interleukin-1β induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis

Yasuyuki Shigematsu, Tohru Niwa, Emil Rehnberg, Takeshi Toyoda, Satoshi Yoshida, Akiko Mori, Mika Wakabayashi, Yoichiro Iwakura, Masao Ichinose, Yong Joon Kim, Toshikazu Ushijima

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59 Citations (Scopus)


Interleukin-1β (Il1b) is considered to be involved in Helicobacter pylori (HP)-induced human gastric carcinogenesis, while the role of its polymorphisms in gastric cancer susceptibility remains controversial. Here, we aimed to clarify the role of HP infection-induced IL1B in gastric inflammation and carcinogenesis using Il1b-/- (Il1b-null) mice. In gastric mucosa of the Il1b+/+ (WT) mice, HP infection induced Il1b expression and severe inflammation. In contrast, in Il1b-null mice, recruitment of neutrophils and macrophages by HP infection was markedly suppressed. In a carcinogenicity test, the multiplicity of gastric tumors was significantly suppressed in the. Il1b-null mice (58% of WT; P<. 0.005). Mechanistically, HP infection induced NF-κB activation both in the inflammatory and epithelial cells in gastric mucosae, and the activation was attenuated in the Il1b-null mice. Accordingly, increased proliferation and decreased apoptosis of gastric epithelial cells induced by HP infection in the WT mice were attenuated in the Il1b-null mice. These results demonstrated that the IL1B physiologically induced by HP infection enhanced gastric carcinogenesis by affecting both inflammatory and epithelial cells.

Original languageEnglish
Pages (from-to)141-147
Number of pages7
JournalCancer Letters
Issue number1
Publication statusPublished - 2013 Oct 28

Bibliographical note

Funding Information:
We thank Dr. Toshio Imai and National Cancer Center Research Core Facility for preparation of sections in this study. Y.S. is a recipient of Research Resident Fellowships from the Foundation for Promotion of Cancer Research. This work was supported by Grants-in-Aid for the Third-Term Comprehensive Cancer control Strategy from the Ministry of Health, Labor and Welfare, Japan; and by the Global Research Laboratory Program from Korea Foundation for International Cooperation of Science & Technology.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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