title: Metallothionein is a crucial protective factor against Helicobacter pylori-induced gastric erosive lesions in a mouse model.
abstract: Infection with the gastric pathogen Helicobacter pylori (H. pylori) causes chronic gastritis, peptic ulcer, and gastric adenocarcinoma. These diseases are associated with production of reactive oxygen species (ROS) from infiltrated macrophages and neutrophiles in inflammatory sites. Metallothionein (MT) is a low-molecular-weight, cysteine-rich protein that can act not only as a metal-binding protein, but also as a ROS scavenger. In the present study, we examined the role of MT in the protection against H. pylori-induced gastric injury using MT-null mice. Female MT-null and wild-type mice were challenged with H. pylori SS1 strain, and then histological changes were evaluated with the updated Sydney grading system at 17 and 21 wk after challenge. Although the colonization efficiency of H. pylori was essentially the same for MT-null and wild-type mice, the scores of activity of inflammatory cells were significantly higher in MT-null mice than in wild-type mice at 17 wk after challenge. Histopathological examination revealed erosive lesions accompanied by infiltration of inflammatory cells in the infected MT-null mice but not in wild-type mice. Furthermore, activation of NF-kappaB and expression of NF-kappaB-mediated chemokines such as macrophage inflammatory protein-1alpha and monocytes chemoattractant protein-1 in gastric cells were markedly higher in MT-null mice than in wild-type mice. These results suggest that MT in the gastric mucosa might play an important role in the protection against H. pylori-induced gastric ulceration.
authors.affiliation: Laboratory Animal Research Center, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Mita
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimada
authors.forename: Mina
authors.initials: M
authors.lastname: Okajima
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Azuma
authors.forename: Junko S
authors.initials: JS
authors.lastname: Suzuki
authors.forename: Kou
authors.initials: K
authors.lastname: Sakabe
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Himeno
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D019610:Cytoprotection; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D007962:Leukocytes / Q000378:metabolism / Q000382:microbiology; D008668:Metallothionein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013276:Stomach Ulcer / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; C491054:Mt2 protein, mouse; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C525355:metallothionein-1, mouse; D008668:Metallothionein