Higher concentration of matrix-metalloproteinase 1 (interstitial collagenase) in H. pylori-compared to NSAID-induced gastric ulcers.
OBJECTIVE
Matrix metalloproteinases (MMPs) are implicated in the tissue destruction associated with inflammatory diseases. We postulated a causal involvement of MMP-1 in ulcerogenesis and quantified therefore the MMP-1 concentrations in biopsies of human gastric ulcers and the surrounding mucosa. Further, we correlated them with the individual ulcer etiology.


METHODS
During upper endoscopy biopsy specimens of the ulcer and surrounding normal mucosa were taken from 45 patients with gastric ulcers of different etiology (Helicobacter pylori, NSAID-intake, both or none of these). MMP-1 concentration was measured using a MMP-1 ELISA in 35 patients, western blot was performed in the remaining 10 patients.


RESULTS
In general, median expression of MMP-1 in the ulcer tissue was significantly increased compared to the surrounding mucosa (16.8 [4.7-33.4] vs. 10.9 [2.8-17.8] ng/mg protein) (p < 0.001). Western blot analysis revealed increased concentration of the active forms of MMP-1 in ulcer tissue. Interestingly, the MMP-1 concentration was significantly higher in 15 H.p.-induced ulcers compared to 19 NSAID-induced ones: 19.3 (8.3-33.2) vs. 11.4 (4.7-33.4) ng/mg protein, p = 0.0354).


CONCLUSIONS
MMP-1-expression in the ulcer tissue depends on the ulcer etiology. However, MMP-1 does not seem to be causally involved in ulcerogenesis. In NSAID-induced ulcers the MMP-1-synthesis may be suppressed by NSAID-induced decrease of mucosal prostaglandin concentration.
Menges
M
M
Department of Internal Medicine II, Saarland University, Homburg, Germany. inmmen@med-rz.uni-sb.de
Chan
C C
CC
Zeitz
M
M
Stallmach
A
A
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001706:Biopsy; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005773:Gastroscopy; D016481:Helicobacter Infections / Q000175:diagnosis* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012016:Reference Values; D013276:Stomach Ulcer / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020781:Matrix Metalloproteinase 1