Interleukin-1β induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis.
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 theIl1b-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.
Division of Epigenomics, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Yasuyuki
Y
Shigematsu
Tohru
T
Niwa
Emil
E
Rehnberg
Takeshi
T
Toyoda
Satoshi
S
Yoshida
Akiko
A
Mori
Mika
M
Wakabayashi
Yoichiro
Y
Iwakura
Masao
M
Ichinose
Yong-Joon
YJ
Kim
Toshikazu
T
Ushijima
D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000276:immunology*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000276:immunology; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology; D007111:Immunity, Cellular; D053583:Interleukin-1beta / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D013274:Stomach Neoplasms / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015533:Transcriptional Activation
D053583:Interleukin-1beta; D016328:NF-kappa B
GC; Gastric cancer; HP; Helicobacter pylori; Helicobacter pylori infection; IHC; Inflammation; Interleukin-1β; MNU; N-methyl-N-nitrosourea; NF-κB; gastric cancer; immunohistochemistry; nuclear factor-κB