Neonatal co-infection with Helicobacter species markedly accelerates the development of inflammation-associated colonic neoplasia in IL-10-/-mice
Neonatal co-infection with Helicobacter species markedly accelerates the development of inflammation-associated colonic neoplasia in IL-10-/-mice
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DOI：
10.1111/j.1523-5378.2007.00552.x
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发表时间：
2007-12-01
期刊：
影响因子：
4.4
通讯作者：
Marchuk, Douglas
中科院分区：
文献类型：
--
作者：
Hale, Laura P.;Perera, Dinushi;Marchuk, Douglas
背景：炎症性肠病（IBD）被认为是一种发生在遗传易感宿主体内的针对肠道细菌的异常免疫反应。患有IBD的人和小鼠发生结肠肿瘤的风险明显增加。然而，在常用的IBD小鼠模型中，炎症相关结肠肿瘤发展所需的较长准备时间减慢了有效化学预防疗法的发展。材料与方法：在免疫调节细胞因子白细胞介素(IL)-10缺乏的小鼠中，采用新生儿同时感染伤寒幽门螺杆菌和啮齿幽门螺杆菌触发IBD的发生。用组织学方法测定结肠炎症的严重程度和肿瘤的发生率。结果：IL-10（-/-）小鼠在新生儿感染伤寒杆菌和啮齿鼠后表现出早发性、严重的结肠炎症。炎症相关结肠肿瘤的发生率在平均年龄21±2周时接近95%。在这个模型中，内啡肽（一种tgf - β的辅助受体）的突变并不影响IBD的严重程度或肿瘤的发生率。结论：IL-10（-/-）小鼠在新生儿同时感染伤寒嗜血杆菌和啮齿鼠后迅速发生严重的结肠炎症和结肠多发肿瘤病变，使该模型非常适合于研究炎症相关结肠癌的机制及其化学预防。
Background: Inflammatory bowel disease (IBD) is hypothesized to represent an aberrant immune response against enteric bacteria that occurs in a genetically susceptible host. Humans and mice with IBD are at markedly increased risk for colonic neoplasia. However, the long lead time required before development of inflammation-associated colon neoplasia in commonly used murine models of IBD slows the development of effective chemopreventative therapies. Materials and methods: Neonatal coinfection with Helicobacter typhlonius and Helicobacter rodentium was used to trigger the onset of IBD in mice deficient in the immunoregulatory cytokine interleukin (IL)-10. The severity of colon inflammation and incidence of neoplasia was determined histologically. Results: IL-10(-/-)mice demonstrated early onset, severe colon inflammation following neonatal infection with H. typhlonius and H. rodentium. The incidence of inflammation-associated colon neoplasia was similar to 95% at a mean age of 21 +/- 2 weeks. Mutation of endoglin, an accessory receptor for TGF-beta, did not affect the severity of IBD or the incidence of neoplasia in this model. Conclusions: The rapid onset of severe colon inflammation and multiple neoplastic lesions in the colons of IL-10(-/-) mice neonatally coinfected with H. typhlonius and H. rodentium makes this model well-suited for investigating the mechanisms involved in inflammation-associated colon cancer as well as its chemoprevention.