Helicobacter pylori upregulates matrilysin (MMP-7) in epithelial cells in vivo and in vitro in a Cag dependent manner.
OBJECTIVE
Matrix metalloproteinase-7 (MMP-7) is important in normal and pathological remodelling of epithelial-matrix interactions, and is upregulated in gastric cancer. Helicobacter pylori infection is the first stage in gastric carcinogenesis, and therefore our aim was to determine if H pylori upregulated gastric MMP-7 expression and if this was affected by strain virulence.


METHODS
We took gastric biopsy specimens at endoscopy from H pylori infected (n = 17) and uninfected (n = 18) patients and assessed MMP-7 expression by ELISA, real time polymerase chain reaction (PCR), and immunohistochemistry (concentrating on epithelial cells in the proliferative zone). We PCR typed H pylori for cagE and vacA. We performed H pylori/cell line coculture studies with wild-type pathogenic and non-pathogenic H pylori strains and with CagE(-) and VacA(-) isogenic mutants.


RESULTS
Gastric biopsy specimens from H pylori+ patients expressed higher levels of MMP-7 at the protein and mRNA levels in the antrum and corpus (for example, by ELISA: H pylori+ 0.182 OD units vH pylori- 0.059; p = 0.009 antrum). Epithelial cells from H pylori+ patients stained more intensely for MMP-7 than those from uninfected patients, including in the proliferative zone containing pluripotent cells (p<0.03 antrum, p<0.04 body). Upregulation of MMP-7 in epithelial cells was confirmed at the protein and mRNA levels by H pylori/cell line coculture. These experiments also showed that MMP-7 upregulation was dependent on an intact H pyloricag pathogenicity island but not on the vacuolating cytotoxin.


CONCLUSIONS
We speculate that increased expression of MMP-7 in H pylori gastritis may contribute to gastric carcinogenesis.
Bebb
J R
JR
Division of Gastroenterology and Institute of Infections, Immunity, and Inflammation, University Hospital, Nottingham, UK.
Letley
D P
DP
Thomas
R J
RJ
Aviles
F
F
Collins
H M
HM
Watson
S A
SA
Hand
N M
NM
Zaitoun
A
A
Atherton
J C
JC
D000368:Aged; D001426:Bacterial Proteins / Q000032:analysis; D002478:Cells, Cultured; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000201:enzymology*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology*; D016481:Helicobacter Infections / Q000201:enzymology*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D001426:Bacterial Proteins; D009687:Nuclear Proteins; C074689:VacA protein, Helicobacter pylori; D020783:Matrix Metalloproteinase 7