Long-term morpho-functional development of Helicobacter pylori-induced gastritis in Mongolian gerbils.
OBJECTIVE
Epidemiological studies have shown that Helicobacter pylori infection with associated chronic gastritis is the main risk factor for development of gastric cancer. The aim of this study was to investigate the long-term development of H. pylori-induced gastritis in Mongolian gerbils in terms of morphology, gastrin secretion, epithelial proliferation and gene expression of pro-inflammatory cytokines.


METHODS
A total of 133 gerbils were inoculated with H. pylori and 62 served as controls. The gerbils were killed at different time-points between 6 and 94 weeks after inoculation. Serum concentrations of anti-H. pylori IgG and gastrin were determined by enzyme-linked immunoabsorbent assay (ELISA) and radioimmunoassay (RIA), respectively. Epithelial proliferation was evaluated immunohistochemically after labeling with 5-bromo-2'-deoxy-uridine. Gene expression of beta-actin, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Histological parameters of gastritis were assessed semiquantitatively and expressed as a "gastritis score".


RESULTS
Serum concentrations of anti-H. pylori IgG and gastrin increased over time. Epithelial proliferation in the antrum was increased 6 weeks after inoculation, followed by increased proliferation in the corpus 32 weeks after inoculation. Gene expression of IL-1beta and TNF-alpha were increased in H. pylori-infected gerbils. Beta-actin was not a reliable endogenous control for RT-PCR. With time, gastritis expanded from the antrum to the corpus and the gastritis score increased to reach a peak 32 weeks after inoculation. Pseudopyloric metaplasia (loss of specialized cells) was a characteristic feature in the corpus mucosa. Gastric ulcers, but neither dysplasia nor carcinoma, were observed during 94 weeks of infection.


CONCLUSIONS
Long-term H. pylori infection in Mongolian gerbils led to progressive gastritis, glandular atrophy, hypergastrinemia, increased epithelial proliferation and elevated gene expression of pro-inflammatory cytokines.
Sun
Yi-Qian
YQ
Department of Biomedicine and Surgery, University of Linköping, and Pathology Research Department, Ryhov Hospital, Fönköping, Sweden. yisun@ibk.liu.se
Petersson
Frederik
F
Monstein
Hans-Jürg
HJ
Söderholm
Johan D
JD
Rehfeld
Jens F
JF
Borch
Kurt
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005755:Gastrins / Q000097:blood; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology*; D015964:Gene Expression Regulation, Bacterial; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D011706:Pyloric Antrum / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D005755:Gastrins; D007074:Immunoglobulin G; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha