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.
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.
Authors: Goo Lee; Tatiana Goretsky; Elizabeth Managlia; Ramanarao Dirisina; Ajay Pal Singh; Jeffrey B Brown; Randal May; Guang-Yu Yang; Josette William Ragheb; B Mark Evers; Christopher R Weber; Jerrold R Turner; Xi C He; Rebecca B Katzman; Linheng Li; Terrence A Barrett Journal: Gastroenterology Date: 2010-05-24 Impact factor: 22.682
Authors: Deanna D Nguyen; Suresh Muthupalani; Jeremy A Goettel; Michelle A Eston; Melissa Mobley; Nancy S Taylor; Amanda McCabe; Romela Marin; Scott B Snapper; James G Fox Journal: Inflamm Bowel Dis Date: 2013-09 Impact factor: 5.325
Authors: Charlie C Hsu; Jisun Paik; Piper M Treuting; Audrey Seamons; Stacey M Meeker; Thea L Brabb; Lillian Maggio-Price Journal: Comp Med Date: 2014-08 Impact factor: 0.982
Authors: Jennifer Ls Lofgren; Michael Esmail; Melissa Mobley; Amanda McCabe; Nancy S Taylor; Zeli Shen; Susan Erdman; Christine Hewes; Mark T Whary; James G Fox Journal: J Am Assoc Lab Anim Sci Date: 2012-07 Impact factor: 1.232