title: Helicobacter pylori-elicited induction in gastric mucosal matrix metalloproteinase-9 (MMP-9) release involves ERK-dependent cPLA2 activation and its recruitment to the membrane-localized Rac1/p38 complex.
abstract: Matrix metalloproteinases (MMPs) are a family of endopeptidases implicated in a wide rage of degenerative and inflammatory diseases, including Helicobacter pylori-associated gastritis, and gastric and duodenal ulcer. As gastric mucosal inflammatory responses to H. pylori are characterized by the rise in MMP-9 production, as well as the induction in mitogen-activated protein kinase (MAPK) and Rac1 activation, we investigated the role of Rac1/MAPK in the processes associated with the release of MMP-9. We show that H. pylori LPS-elicited induction in gastric mucosal MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cytosolic phospholipase A2 (cPLA2). Further, we demonstrate that the LPS-induced MMP-9 release requires ERK-mediated phosphorylation of cPLA2 on Ser(505) that is essential for its membrane localization with Rac1, and that this process necessitates p38 participation. Moreover, we reveal that the activation and membrane translocation of p38 to the Rac1-GTP complex plays a pivotal role in cPLA2-dependent enhancement in MMP-9 release. Hence, our findings provide a strong evidence for the role of ERK/cPLA2 and Rac1/p38/cPLA2 cascade in H. pylori LPS-induced up-regulation in gastric mucosal MMP-9 release.
authors.affiliation: Research Center, C875, Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA. slomiabr@sdm.rutgers.edu.
authors.forename: B L
authors.initials: BL
authors.lastname: Slomiany
authors.affiliation: Research Center, C875, Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA.
authors.forename: A
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; D054513:Group IV Phospholipases A2; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: ERK; Gastric mucosa; H. pylori LPS; Rac1; cPLA2 activation MMP-9 release; p38