title: Increased production of matrix metalloproteinases in Helicobacter pylori-associated human gastritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medical Microbiology and Immunology, Göteborg University, Sweden. philip.bergin@microbio.gu.se
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bergin
authors.forename: Edebo
authors.initials: E
authors.lastname: Anders
authors.forename: Wen
authors.initials: W
authors.lastname: Sicheng
authors.forename: Johnsson
authors.initials: J
authors.lastname: Erik
authors.forename: Andersson
authors.initials: A
authors.lastname: Jennie
authors.forename: Lönroth
authors.initials: L
authors.lastname: Hans
authors.forename: Michetti
authors.initials: M
authors.lastname: Pierre
authors.forename: Pan-Hammarström
authors.initials: PH
authors.lastname: Qiang
authors.forename: Quiding-Järbrink
authors.initials: QJ
authors.lastname: Marianne
mesh_terms: D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9