M Menges1, C C Chan, M Zeitz, A Stallmach. 1. Department of Internal Medicine II, Saarland University, Homburg, Germany. inmmen@med-rz.uni-sb.de
Abstract
BACKGROUND/ 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). CONCLUSION: 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.
BACKGROUND/ 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 humangastric 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). CONCLUSION: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.