Abstract
To test the hypothesis that Helicobacter pylori regulates gastric cell secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), culture media from infected and uninfected human gastric adenocarcinoma (AGS) cells were analyzed by zymography, MMP activity assays, and immunoblotting. AGS cells secreted gelatinolytic (prominently 90 kDa) 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 gelatinolytic (~35 kDa) and caseinolytic (22 kDa) activities. Infection also increased both basal secretion and activation of MMP-1 and MMP-3, enhanced TIMP-3 secretion, and increased the formation of MMP-3/TIMP-3 complexes. TIMP-1 and TIMP-2 secretion were unchanged. Normal AGS cells showed a pancellular distribution of TIMP-3, with redistribution of immunoreactivity 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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / enzymology
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Adenocarcinoma / microbiology
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Bacterial Proteins / analysis
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Bacterial Proteins / metabolism
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Caseins / metabolism
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Culture Media, Conditioned / chemistry
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Culture Media, Conditioned / metabolism
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Electrophoresis, Polyacrylamide Gel
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Enzyme Activation
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Epithelial Cells / enzymology*
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Epithelial Cells / microbiology
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Helicobacter Infections / enzymology*
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Helicobacter pylori / enzymology*
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Humans
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Matrix Metalloproteinase 1 / analysis
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Matrix Metalloproteinase 1 / metabolism
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Matrix Metalloproteinase 3 / analysis
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Matrix Metalloproteinase 3 / metabolism
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Metalloendopeptidases / analysis
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Metalloendopeptidases / metabolism*
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Stomach Neoplasms / enzymology
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Stomach Neoplasms / microbiology
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Tissue Inhibitor of Metalloproteinase-1 / analysis
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Tissue Inhibitor of Metalloproteinase-1 / metabolism
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Tissue Inhibitor of Metalloproteinase-2 / analysis
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Tissue Inhibitor of Metalloproteinase-2 / metabolism
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Tissue Inhibitor of Metalloproteinase-3 / analysis
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Tissue Inhibitor of Metalloproteinase-3 / metabolism
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Tissue Inhibitor of Metalloproteinases / analysis
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Tissue Inhibitor of Metalloproteinases / metabolism*
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Tumor Cells, Cultured
Substances
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Bacterial Proteins
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Caseins
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Culture Media, Conditioned
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Tissue Inhibitor of Metalloproteinase-1
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Tissue Inhibitor of Metalloproteinase-3
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Tissue Inhibitor of Metalloproteinases
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Tissue Inhibitor of Metalloproteinase-2
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Metalloendopeptidases
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 1