Significance of cell-surface expression of matrix metalloproteinases and their inhibitors on gastric epithelium and infiltrating mucosal lymphocytes in progression of helicobacter pylori-associated gastritis

Abstract

Background: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) have recently been shown to be important in tissue breakdown and remodeling in gut with inflammatory bowel disease. The role of MMPs and TIMPs remains largely unexplored in Helicobacter pylori-associated gastritis (HAG). The aim of this study was to investigate the expression of these proteolytic enzymes in HAG. Methods: Cell-surface or/and intracellular expression of MMP-2, 7, 9 and MT1-MMP and TIMPs (TIMP-2 and -4) was determined in gastric epithelium and infiltrative mucosal lymphocytes (IML) in single endoscopic biopsies from H. pylori-infected (n = 25) and uninfected (n = 15) patients. The quantitative analysis was based on the percentage of positive cells detected by flow cytometry. Results: Secreted MMPs and TIMPs as well as membrane type 1-MMP were shown to be localized mainly on the cell surface of both epithelial cells and IML in HAG. H. pylori significantly up-regulated the cell-surface expression not only of MMPs, but also of TIMPs on IML within tissues. The expression of these molecules on IML was correlated with the grade of gastritis. Conclusions: MMPs and TIMPs expressed on gastric epithelium and H. pylori-antigen(s)-stimulated IML may be implicated in mucosal degradation and remodeling of the stomach. These might contribute to the pathogenesis and progression of atrophy and intestinal metaplasia of gastric mucosa.