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Cag Pathogenicity Island-independent Up-regulation of Matrix Metalloproteinases-9 and -2 Secretion and Expression in Mice by Helicobacter pylori Infection

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Cag Pathogenicity Island-independent Up-regulation of Matrix Metalloproteinases-9 and -2 Secretion and Expression in Mice by Helicobacter pylori Infection
 
Creator Kundu, Parag
Mukhopadhyay, Asish K
Patra, Rajashree
Banerjee, Aditi
Berg, Douglas E
Swarnakar, Snehasikta
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description Helicobacter pylori cag pathogenicity island (PAI) is a major determinant of gastric injury via induction of several matrix metalloproteinases (MMPs). In the present study, we examined the influence of the cag PAI on gastric infection and MMP-9 production in mice and in cultured cells. A new mouse colonizing Indian H. pylori strain (AM1) that lacks the cag PAI was used to study the cag PAI importance in inflammation. Groups of C57BL/6 mice were inoculated separately with H. pylori strains AM1 and SS1 (cag�), gastric tissues were histologically examined, and bacterial colonization was scored by quantitative culture. Mice infected with either cag� or cag� H. pylori strains showed gastric inflammation and elevated MMP-3 production. Significant up-regulation of pro-MMP-9 secretion and gene expression in H. pylori infected gastric tissues indicate dispensability of cag PAI for increased pro-MMP-9 secretion and synthesis in mice. In agreement, cell culture studies revealed that both AM1 and SS1 were equipotent in pro-MMP-9 induction in human gastric epithelial cells. Both strains showed moderate increase in MMP-2 activity in vivo and in vitro. In addition, increased secretion of tumor necrosis factor (TNF)-�, interleukin (IL)-1�, and IL-6 induced pro- MMP-9 secretion and synthesis in AM1 or SS1 strain-infected mice suggesting elicitation of pro-inflammatory cytokines by both cag� and cag� genotype. Moreover, tissue inhibitors of metalloproteinase-1 expression were decreased with increase in pro-MMP-9 induction. These data show that H. pylori may act through different pathways other than cag PAI-mediated for gastric inflammation and contribute to upregulation of MMP-9 via pro-inflammatory cytokines.
 
Date 2006
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/479/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY%2C281(_45)%2C_34651%2D34662%2C2006_[16].pdf
Kundu, Parag and Mukhopadhyay, Asish K and Patra, Rajashree and Banerjee, Aditi and Berg, Douglas E and Swarnakar, Snehasikta (2006) Cag Pathogenicity Island-independent Up-regulation of Matrix Metalloproteinases-9 and -2 Secretion and Expression in Mice by Helicobacter pylori Infection. The Journal of Biological Chemistry, 281 (45). pp. 34651-34662.
 
Relation htpp://dx.doi.org/10.1074/jbc.M604574200
http://www.eprints.iicb.res.in/479/