Division of Epigenomics, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Cancer Lett. 2013 Oct 28;340(1):141-7. doi: 10.1016/j.canlet.2013.07.034. Epub 2013 Aug 3.
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.
白细胞介素-1β（IL-1β）被认为参与了幽门螺杆菌（HP）诱导的人类胃癌发生，而其多态性在胃癌易感性中的作用仍存在争议。在这里，我们旨在使用 Il1b（-/-）（Il1b-/-）小鼠阐明 HP 感染诱导的 IL1B 在胃炎症和癌变中的作用。在 Il1b（+/+）（WT）小鼠的胃黏膜中，HP 感染诱导 Il1b 表达和严重炎症。相比之下，在 Il1b-/- 小鼠中，HP 感染引起的中性粒细胞和巨噬细胞的募集明显受到抑制。在致癌性试验中，Il1b-/- 小鼠的胃肿瘤数量明显减少（WT 的 58%；P<0.005）。在机制上，HP 感染诱导了胃黏膜中炎症和上皮细胞中的 NF-κB 激活，而 Il1b-/- 小鼠中的激活受到抑制。因此，在 WT 小鼠中，HP 感染诱导的胃上皮细胞增殖增加和凋亡减少受到了抑制。这些结果表明，HP 感染生理性诱导的 IL1B 通过影响炎症细胞和上皮细胞来增强胃癌的发生。
