Dual infection with helicobacter bilis and helicobacter hepaticus in P-Glycoprotein-Deficient mdr1a–/– mice results in colitis that progresses to dysplasia

Maggio-Price, Lillian, Bielefeldt-Ohmann, Helle, Treuting, Piper, Iritani, Brian M., Zeng, Weiping, Nicks, Andrea, Tsang, Mark, Shows, Donna, Morrisey, Phil and Viney, Joanne L. (2005) Dual infection with helicobacter bilis and helicobacter hepaticus in P-Glycoprotein-Deficient mdr1a–/– mice results in colitis that progresses to dysplasia. American Journal of Pathology, 166 6: 1793-1806. doi:10.1016/S0002-9440(10)62489-3


Author Maggio-Price, Lillian
Bielefeldt-Ohmann, Helle
Treuting, Piper
Iritani, Brian M.
Zeng, Weiping
Nicks, Andrea
Tsang, Mark
Shows, Donna
Morrisey, Phil
Viney, Joanne L.
Title Dual infection with helicobacter bilis and helicobacter hepaticus in P-Glycoprotein-Deficient mdr1a–/– mice results in colitis that progresses to dysplasia
Journal name American Journal of Pathology   Check publisher's open access policy
ISSN 0002-9440
1525-2191
Publication date 2005-06-01
Sub-type Article (original research)
DOI 10.1016/S0002-9440(10)62489-3
Volume 166
Issue 6
Start page 1793
End page 1806
Total pages 14
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Subject 07 Agricultural and Veterinary Sciences
0707 Veterinary Sciences
0702 Animal Production
Abstract Patients with inflammatory bowel disease (IBD) are at increased risk for developing high-grade dysplasia and colorectal cancer. Animal IBD models that develop dysplasia and neoplasia may help elucidate the link between inflammation and colorectal cancer. Mdr1a–/– mice lack the membrane efflux pump p-glycoprotein and spontaneously develop IBD that can be modulated by infection with Helicobacter sp: H. bilis accelerates development of colitis while H. hepaticus delays disease. In this study, we determined if H. hepaticus infection could prevent H. bilis-induced colitis. Unexpectedly, a proportion of dual-infected mdr1a–/– mice showed IBD with foci of low- to high-grade dysplasia. A group of dual-infected mdr1a–/– animals were maintained long term (39 weeks) by intermittent feeding of medicated wafers to model chronic and relapsing disease. These mice showed a higher frequency of high-grade crypt dysplasia, including invasive adenocarcinoma, possibly because H. hepaticus, in delaying the development of colitis, allows time for transformation of epithelial cells. Colonic epithelial preparations from co-infected mice showed increased expression of c-myc (5- to 12-fold) and interleukin-1{alpha}/ß (600-fold) by real-time polymerase chain reaction relative to uninfected wild-type and mdr1a–/– animals. This animal model may have particular relevance to human IBD and colorectal cancer because certain human MDR1 polymorphisms have been linked to ulcerative colitis and increased risk for colorectal cancer.
Keyword Inflammatory bowel disease
Dysplasia
Colorectal Cancer
Neoplasia
Inflammation
Ulcerative Colitis
Human IBD
Epithelial cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Available online 14 December 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
ERA 2012 Admin Only
School of Veterinary Science Publications
 
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Created: Sat, 05 Dec 2009, 01:54:20 EST by Rosalind Blair on behalf of Faculty Of Nat Resources, Agric & Veterinary Sc