Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 -/- C57BL6 x Sv129 Helicobacter pylori-infected mice.
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.
Fox
James G
JG
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. jgfox@mit.edu
Rogers
Arlin B
AB
Whary
Mark T
MT
Ge
Zhongming
Z
Ohtani
Masa
M
Jones
Evelyn Kurt
EK
Wang
Timothy C
TC
D000818:Animals; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D006965:Hyperplasia / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood; D008679:Metaplasia / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000235:genetics / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D011230:Precancerous Conditions / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D011706:Pyloric Antrum / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D000071164:Trefoil Factor-2
D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; C000604007:TFF2 protein, human; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2; D007371:Interferon-gamma