Higher concentration of matrix-metalloproteinase 1 (interstitial collagenase) in H. pylori-compared to NSAID-induced gastric ulcers

Summary

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.

Höhere Konzentration der Matrix-Metalloproteinase 1 (interstitielle Kollagenase) in H.pylori - im Vergleich zu NSAR-induzierten Magenulzera

Hintergrund und Ziele: Matrix-Metalloproteinasen (MMP) sind an der Gewebezerstörung im Rahmen entzündlicher Prozesse beteiligt. Wir postulierten eine kausale Beteiligung von MMP-1 an der Ulzerogenese und quantifizierten daher die MMP-1-Konzentrationen in Biopsien aus Magenulzera und der umgebenden Mukosa. Weiterhin korrelierten wir sie mit der individuellen Ulkusgenese.

Methoden: Während der Gastroskopie wurden von 45 Patienten mit Magenulzera verschiedener Ätiologie (Helicobacter pylori, NSAR-Einnahme, beide oder keine von diesen) Gewebeproben aus dem Ulkus und der umgebenden, normal erscheinenden Mukosa entnommen. Die MMP-1-Konzentration wurde mit einem ELISA bei 35 Patienten bestimmt, bei den übrigen 10 wurde ein Western-Blot-Test durchgeführt.

Ergebnisse: Bei Betrachtung der Gesamtgruppe war die mediane MMP-1-Expression im Ulkusgewebe im Vergleich zur Umgebung signifikant erhöht (16,8 [4] [7 33] [4] vs. 10,9 [2] [8 17] [8] ng/ml Protein, p < 0,001). Die Western-Blot-Analyse zeigte eine erhöhte Konzentration der aktiven MMP-1-Formen im Ulkusgewebe. Interessanterweise war die MMP-1-Konzentration in 15 H.-p.-induzierten Ulzera signifikant höher als bei 19 NSAR-induzierten Ulzera (19,3 [8,3-33,2] vs. 11,4 [5,0-22,4], p = 0,0354).

Schlussfolgerung: Die MMP-1-Expression im Ulkusgewebe ist abhängig von der Ulkusätiologie, MMP-1 scheint jedoch nicht kausal in die Ulzerogenese involviert zu sein. Bei NSAR-induzierten Ulzera wird die MMP-1-Synthese vermutlich durch den NSAR-bedingten Abfall der mukosalen Prostaglandinkonzentration gehemmt.

Key words

Matrix-Metalloproteinases - Interstitial Collagenase - Gastric Ulcers - Ulcerogenesis - Tissue Repair - NSAID - Helicobacter Pylori

Schlüsselwörter

Matrix-Metalloproteinasen - interstitielle Kollagenase - Magenulzera - Ulzerogenese - Wundheilung - NSAR - Helicobacter pylori

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