title: CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model.
abstract: 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 cagA (DeltacagA) or cagE (DeltacagE) 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-IkappaBalpha, and phospho-Erk was also performed. All of the bacterial strains colonized the gerbil stomach at similar densities; however, the DeltacagA 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 cagA. The DeltacagA mutant induced less phosphorylation of IkappaBalpha and Erk, and less expression of interferon-gamma and interleukin-1beta 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.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Shibata
authors.forename: Y
authors.initials: Y
authors.lastname: Hirata
authors.forename: S
authors.initials: S
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Ogura
authors.forename: T
authors.initials: T
authors.lastname: Ohmae
authors.forename: A
authors.initials: A
authors.lastname: Yanai
authors.forename: Y
authors.initials: Y
authors.lastname: Mitsuno
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaji
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Kawabe
authors.forename: M
authors.initials: M
authors.lastname: Omata
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D005756:Gastritis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016480:Helicobacter pylori / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007249:Inflammation; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D013997:Time Factors
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D016328:NF-kappa B; C080866:cagA protein, Helicobacter pylori; D020928:Mitogen-Activated Protein Kinases