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(American Journal of Pathology. 2007;171:1520-1528.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070249

Accelerated Progression of Gastritis to Dysplasia in the Pyloric Antrum of TFF2^–/– C57BL6 x Sv129 Helicobacter pylori-Infected Mice

James G. Fox^*, Arlin B. Rogers^*, Mark T. Whary^*, Zhongming Ge^*, Masa Ohtani^*, Evelyn Kurt Jones and Timothy C. Wang

From the Division of Comparative Medicine,^* Massachusetts Institute of Technology, Cambridge, Massachusetts; the University of Massachusetts Medical Center, Worcester, Massachusetts; and Columbia University, New York, New York

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- 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- in the development of H. pylori-associated premalignancy of the distal stomach.

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