Epithelial and bacterial metalloproteinases and their inhibitors in H-pylori infection of human gastric cells

To test the hypothesis that Helicobacter pylori regulates gastric cell secr etion of matrix metalloproteinases (MMPs) and tissue inhibitors of metallop roteinases (TIMPs), culture media from infected and uninfected human gastri c adenocarcinoma (AGS) cells were analyzed by zymography, MMP activity assa ys, and immunoblotting. AGS cells secreted gelatinolytic (prominently 90 kD a) and caseinolytic (110 kDa) activity together with MMP-1, MMP-3, and TIMP -1, TIMP-2, and TIMP-3 isoforms. H. pylori secreted caseinolytic activity ( 60 kDa), MMP-3-like enzyme activity, and TIMP-3 immunoreactivity. H. pylori infection increased the 110-kDa caseinolytic activity and induced new gela tinolytic (similar to 35 kDa) and caseinolytic (22 kDa) activities. Infecti on also increased both basal secretion and activation of MMP-1 and MMP-3, e nhanced TIMP-3 secretion, and increased the formation of MMP-3/TIMP-3 compl exes. TIMP-1 and TIMP-2 secretion were unchanged. Normal AGS cells showed a pancellular distribution of TIMP-3, with redistribution of immunoreactivit y toward sites of bacterial attachment after H. pylori infection. The data indicate that MMP and TIMP secretion by AGS cells is modulated by H. pylori infection and that host MMP-3 and a TIMP-3 homolog expressed by H. pylori mediate at least part of the host cell response to infection.