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PMID: 17982128 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 -/- C57BL6 x Sv129 Helicobacter pylori-infected mice.

The American journal of pathology ·Vol. 171 ·No. 5 ·2007-11-00 ·Pages 1520-8

Fox JG, Rogers AB, Whary MT, Ge Z, Ohtani M, Jones EK, Wang TC

Abstract

Trefoil factor family 2 (TFF2) is up-regulated in Helicobacter spp.-infected gastric tissues of both humans and mice. To ascertain the biological effects of TFF2 in vivo, TFF2(-/-) C57BL/6 x Sv129 and wild-type (WT) C57BL/6 x Sv129 mice were orally infected with Helicobacter pylori SS1. Mice were evaluated for gastric H. pylori colonization, pathology, and cytokine profiles at 6 and 19 months post inoculation (pi). At 6 months pi, there was a significant difference (P < 0.05) for epithelial criteria (mucosal defects, atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia) in the corpus of TFF2(-/-) versus WT mice. At 19 months pi, a similar statistical difference in epithelial parameters was noted in the antrum of TFF2(-/-) versus WT mice (P < 0.01). All of the TFF2(-/-) H. pylori-infected mice had high-grade antral dysplasia, including gastric intraepithelial neoplasia, which was statistically significant (P < 0.05) compared with the infected WT mice. Levels of interferon-gamma were markedly elevated in the gastric mucosa of infected TFF2(-/-) mice at both 6 and 19 months pi. TFF2 provided a cytoprotective and/or anti-inflammatory effect against the progression of premalignant lesions of the gastric corpus at 6 months pi and in the pyloric antrum in H. pylori-infected mice at 19 months pi. These data support a protective role for TFF2 in part by modulating levels of gastric interferon-gamma in the development of H. pylori-associated premalignancy of the distal stomach.

MeSH Terms
Animals Gastritis/metabolism,microbiology,pathology Helicobacter Infections/metabolism,microbiology,pathology Helicobacter pylori/immunology,physiology Hyperplasia/metabolism,microbiology,pathology Interferon-gamma/blood Metaplasia/metabolism,microbiology,pathology Mice Mice, Inbred C57BL Mice, Knockout Mucins/genetics,physiology Muscle Proteins/genetics,physiology Peptides/genetics,physiology Precancerous Conditions/metabolism,microbiology,pathology Pyloric Antrum/metabolism,microbiology,pathology Trefoil Factor-2
Chemicals
Mucins Muscle Proteins Peptides TFF2 protein, human TFF2 protein, mouse Trefoil Factor-2 Interferon-gamma
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Fox James G
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. [email protected]
Rogers Arlin B
Whary Mark T
Ge Zhongming
Ohtani Masa
Jones Evelyn Kurt
Wang Timothy C
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.2353/ajpath.2007.070249
Email
[email protected]
Published
2007-11-00
Pages
1520-8
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC2043513
Subset
IM
Grants
NCI NIH HHS · R01 CA67529 · United States
NCI NIH HHS · P01 CA26731 · United States
NIDDK NIH HHS · R01 DK060758 · United States
NCI NIH HHS · R01 CA87958 · United States
NIEHS NIH HHS · P30 ES002109 · United States
NIEHS NIH HHS · P30 ES02109 · United States
NCI NIH HHS · P01 CA026731 · United States
NCI NIH HHS · R01 CA067529 · United States
NIDDK NIH HHS · R01 DK60758-07 · United States
NIAID NIH HHS · R01 AI51404 · United States
External Links
PubMed source DOI: 10.2353/ajpath.2007.070249 PMC Full Text View journal details
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