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CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model
Author(s) -
Shibata W,
Hirata Y,
Maeda S,
Ogura K,
Ohmae T,
Yanai A,
Mitsuno Y,
Yamaji Y,
Okamoto M,
Yoshida H,
Kawabe T,
Omata M
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2040
Subject(s) - caga , gerbil , biology , helicobacter pylori , pathogenesis , microbiology and biotechnology , secretion , gastric mucosa , apoptosis , stomach , virulence , immunology , medicine , gene , endocrinology , biochemistry , genetics , ischemia
Helicobacter pylori causes various gastro‐duodenal diseases, including gastric cancer. The CagA protein, an H. pylori virulence factor, induces morphological changes in host cells and may be associated with the development of peptic ulcer and gastric carcinoma. The present study has analysed the role of CagA protein in the pathogenesis of H. pylori infection in the Mongolian gerbil model. Mongolian gerbils were challenged with wild‐type H. pylori strain TN2, which has a functional cag pathogenicity island or isogenic mutants with disrupted cag A (Δ cag A) or cag E (Δ cag E) genes. They were sacrificed at 7, 13, and 25 weeks after inoculation. Pathological changes of the gastric mucosa were determined and apoptosis was assessed by the TUNEL assay. Immunohistochemistry for PCNA, phospho‐IκBα, and phospho‐Erk was also performed. All of the bacterial strains colonized the gerbil stomach at similar densities; however, the Δ cag A mutant induced milder gastritis than did the wild type. The extent of apoptosis and lymphoid follicle formation in the epithelium appeared to depend on intact cag A. The Δ cag A mutant induced less phosphorylation of IκBα and Erk, and less expression of interferon‐ γ and interleukin‐1 β mRNA in the epithelium than did the wild type. It is concluded that CagA protein may be essential for the induction of severe gastritis in the Mongolian gerbil model. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.