BACKGROUND: Helicobacter pylori (H. pylori) infection has been linked to the development of chronic gastritis, duodenal ulcer disease, and gastric cancer. Helicobacter pylori- infected patients and animal models develop hypergastrinemia, chronic gastritis, and gastric atrophy. Since gastrin is an important regulator of gastric acid secretion and cell growth, H. pylori regulation of this hormone has been implicated in its pathogenesis. OBJECTIVES: To investigate the effect of H. pylori on gastrin gene expression in mice and of human bacterial isolates on gastrin mRNA expressed in a human cell line. METHODS: Gastrin mRNA was measured by qRT-PCR in H. pylori-infected mice. H. pylori were co-cultured with AGS cells to study regulation of human gastrin gene expression. Various MAP kinases were implicated in signal transduction from the bacteria using specific inhibitors. Gastrin reporter constructs and gel shift assays were used to map DNA responsive elements. RESULTS: In addition to an increase in gastrin mRNA in H. pylori-infected mice, H. pylori induced the endogenous human gastrin gene through MAP kinase-dependent signaling but not NFκB-dependent signaling. Activation of gastrin through MAPK signaling did not require CagA or VacA virulence factors. Transfection studies demonstrated that a GC-rich motif mediated H. pylori-induction of the gastrin promoter and that the motif inducibly binds Sp1 and Sp3 transcription factors. CONCLUSIONS: Direct contact of live H. pylori bacteria with human cells is sufficient to induce gastrin gene expression.
BACKGROUND:Helicobacter pylori (H. pylori) infection has been linked to the development of chronic gastritis, duodenal ulcer disease, and gastric cancer. Helicobacter pylori- infected patients and animal models develop hypergastrinemia, chronic gastritis, and gastric atrophy. Since gastrin is an important regulator of gastric acid secretion and cell growth, H. pylori regulation of this hormone has been implicated in its pathogenesis. OBJECTIVES: To investigate the effect of H. pylori on gastrin gene expression in mice and of human bacterial isolates on gastrin mRNA expressed in a human cell line. METHODS:Gastrin mRNA was measured by qRT-PCR in H. pylori-infected mice. H. pylori were co-cultured with AGS cells to study regulation of humangastrin gene expression. Various MAP kinases were implicated in signal transduction from the bacteria using specific inhibitors. Gastrin reporter constructs and gel shift assays were used to map DNA responsive elements. RESULTS: In addition to an increase in gastrin mRNA in H. pylori-infected mice, H. pylori induced the endogenous humangastrin gene through MAP kinase-dependent signaling but not NFκB-dependent signaling. Activation of gastrin through MAPK signaling did not require CagA or VacA virulence factors. Transfection studies demonstrated that a GC-rich motif mediated H. pylori-induction of the gastrin promoter and that the motif inducibly binds Sp1 and Sp3 transcription factors. CONCLUSIONS: Direct contact of live H. pylori bacteria with human cells is sufficient to induce gastrin gene expression.
Authors: Abraham M Y Nomura; Guillermo I Pérez-Pérez; James Lee; Grant Stemmermann; Martin J Blaser Journal: Am J Epidemiol Date: 2002-06-01 Impact factor: 4.897
Authors: Mathias Z Strowski; Thorsten Cramer; Georgia Schäfer; Stefan Jüttner; Anna Walduck; Ernestina Schipani; Wolfgang Kemmner; Silja Wessler; Christian Wunder; Matthias Weber; Thomas F Meyer; Bertram Wiedenmann; Thomas Jöns; Michael Naumann; Michael Höcker Journal: FASEB J Date: 2003-11-03 Impact factor: 5.191
Authors: Yana Zavros; Sivaprakash Rathinavelu; John Y Kao; Andrea Todisco; John Del Valle; Joel V Weinstock; Malcolm J Low; Juanita L Merchant Journal: Proc Natl Acad Sci U S A Date: 2003-10-10 Impact factor: 11.205
Authors: Lucinda J Thompson; Stephen J Danon; John E Wilson; Jani L O'Rourke; Nina R Salama; Stanley Falkow; Hazel Mitchell; Adrian Lee Journal: Infect Immun Date: 2004-08 Impact factor: 3.441