Neonatal co-infection with helicobacter species markedly accelerates the development of inflammation-associated colonic neoplasia in IL-10(-/-) mice.

Published

Journal Article

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 approximately 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.

Full Text

Duke Authors

Cited Authors

  • Hale, LP; Perera, D; Gottfried, MR; Maggio-Price, L; Srinivasan, S; Marchuk, D

Published Date

  • December 2007

Published In

Volume / Issue

  • 12 / 6

Start / End Page

  • 598 - 604

PubMed ID

  • 18001399

Pubmed Central ID

  • 18001399

International Standard Serial Number (ISSN)

  • 1083-4389

Digital Object Identifier (DOI)

  • 10.1111/j.1523-5378.2007.00552.x

Language

  • eng

Conference Location

  • England