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.
Bibliographical noteFunding 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
- Cancer Research