HELICOBACTER PYLORI INFECTION IN THE MOUSE MODEL REDUCES METALLOTHIONEIN EXPRESSION

CD Tran, RN Butler H Huynh, F Campbell & P Coyle.
Journal of Gastroenterology and Hepatology (2000), Volume 15; Supplement: J43

Australian Gastroenterology Week, 18-21 October 2000, Hobart, Australia

ABSTRACT:

INTRODUCTION: Metallothionein (MT) is a ubiquitous low molecular weight, cysteine-rich, heavy metal-binding protein involved in metal detoxification and regulation of zinc metabolism. MT can also protect against oxidative damage by sequestering reactive oxygen species (ROS). Helicobacter pylori (Hp) is a gram-negative bacterium affecting about half the world's population, causing gastric inflammation possibly via enhanced production of reactive oxygen species in the gastric epithelium. Thus, MT has the potential to protect against Hp-induced gastritis. The aim of this study was to investigate the relationship between MT and Hp infection in a mouse model.

METHOD: C57BI/6 mice were infected with either 1 x108 Hp (SS1 strain)/ml (mild gastritis) or H. felis (severe gastritis). Hp load was determined by culturing homogenised gastric tissue on Helicobacter-selective agar plates. MT concentration in gastric tissue was determined using the Cd/haemoglobin affinity assay at 1 and 4 or 6 and 12 weeks post Hp and H. felis infection, respectively. Significance (p<0.05) was determined by the Student's t- test or ANOVA followed by Tukey's LSD.

RESULTS: Hp load was significantly increased at 4 weeks (6 x 106 CFU/g tissue; mean) post Hp infection compared to 1 week (3 x 106 CFU/g tissue). MT levels (4.1 ± 0.2 nmol Cd bound/g tissue; mean ± sem) were significantly decreased after 1 week of Hp infection compared to non-infected controls (5.7 ± 0.6). In addition, after 4 weeks of Hp infection, MT levels were further depleted (2.9 ± 0.2) compared to non-infected controls. Similarly, H. felis infection significantly decreased MT levels at 6 and 12 weeks (3.04 ± 0.7 and 3.46 ± 0.2, respectively) compared to controls.

CONCLUSION: These findings suggest that MT degradation may be increased after sequestration of ROS or, alternatively, Hp infection may inhibit the endogenous expression of gastric MT, irrespective of the severity of gastritis. As the exact role of MT in relation to Hp infection is not fully understood, further work characterizing the susceptibility of Hp infection in transgenic mice may help elucidate its role.