Helicobacter-induced gastritis in mice not expressing metallothionein-I and II.
BACKGROUND
Helicobacter pylori a primary cause of gastritis and peptic ulcer disease, is associated with increased production of reactive oxygen species within the gastric mucosa. Metallothionein (MT), a low-molecular-weight, cysteine-rich, metal-binding ligand, has been shown to sequester reactive oxygen species and reduce tissue damage. This study investigates the role of MT in H. pylori-induced gastritis in mice.


METHODS
Control (MT+/+) and MT-null (MT-/-) mice were inoculated with either 1 x 108H. pylori or H. felis, and were infected for 4, 8 and 16 weeks or 8 weeks, respectively. H. pylori load was determined by culture. Myloperoxidase activity and MT levels were also determined.


RESULTS
The stomachs of H. felis-infected mice were more severely inflamed than those of H. pylori-infected mice. H. felis-induced gastritis was more severe (p =.003) in MT-/- than in MT+/+ mice. MT-/- mice also had higher (60%; p <.05) H. pylori loads than MT+/+ mice 4 weeks after infection but not 8 or 16 weeks after infection. Myloperoxidase activity with H. pylori was similar between MT+/+ and MT-/- mice. Thirty-three per cent greater (p <.05) myloperoxidase activity was observed in MT-/- than in MT+/+ mice infected with H. felis. In MT+/+ mice infected with H. pylori, liver MT was increased by 33 and 39% (p <.05) at 8 and 16 weeks, respectively, whereas gastric MT increased by 46% (p <.05) at 4 weeks and declined to baseline levels at 8 and 16 weeks.


CONCLUSIONS
Mice lacking MT are more susceptible to H. pylori colonization and gastric inflammation, indicating that MT may be protective against H. pylori-induced gastritis.
Tran
Cuong D
CD
Gastroenterology Unit, Women's & Children's Hospital, North Adelaide, SA, Australia.
Huynh
Hien
H
van den Berg
Maartje
M
van der Pas
Mechtelt
M
Campbell
M A Fiona
MA
Philcox
Jeffrey C
JC
Coyle
Peter
P
Rofe
Allau M
AM
Butler
Ross N
RN
D000818:Animals; D015169:Colony Count, Microbial; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D044922:Helicobacter felis / Q000472:pathogenicity*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013270:Stomach / Q000382:microbiology / Q000473:pathology
D017382:Reactive Oxygen Species; D008668:Metallothionein; D009195:Peroxidase