title: Neonatal co-infection with helicobacter species markedly accelerates the development of inflammation-associated colonic neoplasia in IL-10(-/-) mice.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. laura.hale@duke.edu
authors.forename: Laura P
authors.initials: LP
authors.lastname: Hale
authors.forename: Dinushi
authors.initials: D
authors.lastname: Perera
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Gottfried
authors.forename: Lillian
authors.initials: L
authors.lastname: Maggio-Price
authors.forename: Sudha
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Douglas
authors.initials: D
authors.lastname: Marchuk
mesh_terms: D000818:Animals; D003092:Colitis / Q000150:complications / Q000235:genetics / Q000382:microbiology*; D003110:Colonic Neoplasms / Q000150:complications / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D000071063:Endoglin; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications*; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000382:microbiology / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016753:Interleukin-10