Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 171, Issue 5, Pages 1520-1528Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2007.070249
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Funding
- NCI NIH HHS [R01 CA67529, P01 CA026731, P01 CA26731, R01 CA067529, R01 CA87958] Funding Source: Medline
- NIAID NIH HHS [R01 AI51404] Funding Source: Medline
- NIDDK NIH HHS [R01 DK60758-07, R01 DK060758] Funding Source: Medline
- NIEHS NIH HHS [P30 ES002109, P30 ES02109] Funding Source: Medline
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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. pyloti 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. pyloti-associated premalignancy of the distal stomach.
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