Increased production of matrix metalloproteinases in Helicobacter pylori-associated human gastritis
Philip J Bergin1, Edebo Anders, Wen Sicheng
1Department of Medical Microbiology and Immunology, Göteborg University, Sweden. philip.bergin@microbio.gu.se
Background And Aims:
Helicobacter pylori infection results in an active, chronic inflammation of the gastric mucosa. Previous studies have highlighted the importance of matrix metalloproteinases (MMPs) in diseases involving mucosal inflammation, prompting us to investigate MMP activity in H. pylori-induced gastritis.
Methods:
Gastric biopsies were obtained from H. pylori-infected and uninfected volunteers, and MMP activity was assessed using substrate gel electrophoresis. MMP production was also evaluated by immunohistochemistry and real time-polymerase chain reaction. In parallel, tissue inhibitors of MMPs (TIMP) levels and TIMP-MMP complexes were examined in corresponding tissues using enzyme-linked immunosorbent assays and Western blotting. Finally, MMP production by gastric macrophages was determined after stimulation with H. pylori.
Results:
Antral mucosa of H. pylori-infected subjects demonstrated a 19-fold higher MMP-9 activity than that of uninfected individuals. MMP-2 was present at lower levels, but was also increased in H. pylori-infected individuals, while there was no difference in the total levels of TIMP-1 and TIMP-2 between the groups of volunteers. Significant numbers of MMP-9-containing cells were only found in the H. pylori-infected antral mucosa. Tissue-resident macrophages were significantly increased in H. pylori-infected individuals, and double-staining showed MMP-9 colocalized to macrophages. Furthermore, gastric macrophages secreted MMP-9 in response to H. pylori bacteria. A corresponding 10-fold increase of gene expression of MMP-9 was seen in patients infected with H. pylori compared to uninfected individuals.
Conclusions:
Helicobacter pylori infection results in a substantial increase in MMP-9 and MMP-2 activity in the gastric mucosa, probably contributed to in large part by tissue-resident macrophages, while no changes were seen in the TIMP levels. The net increase in gastric MMP activity is likely to contribute to tissue damage during H. pylori-associated gastritis.
Insights
Helicobacter pylori infection significantly increases matrix metalloproteinase-9 (MMP-9) and MMP-2 activity in the stomach, primarily due to macrophages. This heightened MMP activity likely contributes to tissue damage in H. pylori gastritis.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Helicobacter pylori infection causes chronic gastric inflammation.
- Matrix metalloproteinases (MMPs) play a role in inflammatory conditions.
Purpose of the Study:
- To investigate MMP activity in H. pylori-induced gastritis.
- To determine the role of macrophages in MMP production during H. pylori infection.
Main Methods:
- Assessed MMP activity using substrate gel electrophoresis on gastric biopsies.
- Evaluated MMP production via immunohistochemistry and real-time PCR.
- Examined tissue inhibitors of MMPs (TIMPs) and MMP complexes using ELISAs and Western blotting.
- Determined MMP production by gastric macrophages stimulated with H. pylori.
Main Results:
- H. pylori infection led to a 19-fold increase in MMP-9 activity and elevated MMP-2 activity in the antral mucosa.
- MMP-9 was localized to macrophages, which were increased in infected individuals.
- Gastric macrophages secreted MMP-9 upon stimulation with H. pylori.
- MMP-9 gene expression increased 10-fold in infected patients.
Conclusions:
- H. pylori infection substantially increases gastric MMP-9 and MMP-2 activity, largely due to tissue-resident macrophages.
- TIMP levels remained unchanged, indicating a net increase in active MMPs.
- Elevated gastric MMP activity likely contributes to tissue damage in H. pylori-associated gastritis.
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