ADAM proteases involved in inflammation are differentially altered in patients with gastritis or ulcer

ADAM metallopeptidase domain (ADAM)9, 10 and 17 have α-secretase activity that regulates ectodomain shedding of factors involved in inflammation, cell proliferation, angiogenesis, and wound healing. The secretase activity of ADAM proteins is known to induce an inflammatory response. However, under certain conditions, a lack of secretase activity may induce inflammation suggesting differential roles of ADAM proteins with secretase activity. To the best of our knowledge, the present study evaluated the changes in α-secretase activity and expression of associated ADAM proteases (ADAM9, 10 and 17) in the gastric mucosa of patients with gastritis and ulcers, for the first time. Gastroduedonal mucosal samples from 42 patients were snap-frozen to determine changes in α-secretase activity. Twenty-four of these patients had gastritis, 9 patients had duedonal ulcers and 9 patients did not have any pathological changes. Paraffin-embedded gastric specimens (n=32) were used for immunohistochemical detection of ADAM9, ADAM10 and ADAM17. α-secretase activity of the gastric mucosa of healthy subjects was significantly higher compared with the uninvolved mucosa of patients with gastritis or ulcer. These results were associated with the immunohistochemical staining results, which demonstrated that ADAM10 expression markedly decreased in glandular epithelial cells and ADAM9 expression was lost in foveolar epithelial cells of gastric mucosa adjacent to ulcer. However, ADAM17 expression was increased in the normal gastric mucosa of patients with bleeding peptic ulcers and in the gastric mucosa adjacent to the ulcer suggesting a counteracting role of ADAM17. Decreased ADAM9 and 10 expression, and an associated decrease in α-secretase activity may predispose to chronic gastritis and ulcer. Further studies are required to determine the possible etiological role of increased ADAM17 expression.