title: Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains.
abstract: Following adhesion of Helicobacter pylori to gastric epithelial cells, intracellular signaling leads to cytokine production, which causes H. pylori-related gastric injury. Two adjacent homologous genes (alpA and alpB), which encode H. pylori outer membrane proteins, are thought to be associated with adhesion and cytokine induction. We co-cultured gastric epithelial cells with wild type H. pylori strains and their corresponding alpA/alpB-deleted mutants (DeltaalpAB). Results were confirmed by complementation. Flow cytometry confirmed that AlpAB was involved in cellular adhesion. Deletion of alpAB reduced interleukin (IL)-6 induction in gastric epithelial cells. Deletion of alpAB reduced IL-8 induction with East Asian but not with Western strains. All AlpAB-positive strains tested activated the extracellular signal-regulated kinase, c-Fos, and cAMP-responsive element-binding protein. Activation of the Jun-N-terminal kinase, c-Jun, and NF-kappaB was exclusive to AlpAB from East Asian strains. DeltaalpAB mutants poorly colonized the stomachs of C57BL/6 mice and were associated with lower mucosal levels of KC and IL-6. Our results suggest that AlpAB may induce gastric injury by mediating adherence to gastric epithelial cells and by modulating proinflammatory intracellular signaling cascades. Known geographical differences in H. pylori-related clinical outcomes may relate to differential effects of East Asian and Western types of AlpAB on NF-kappaB-related proinflammatory signaling pathways.
authors.affiliation: Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Jeng Yih
authors.initials: JY
authors.lastname: Wu
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Beswick
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohno
authors.forename: Stefan
authors.initials: S
authors.lastname: Odenbreit
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reyes
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kita
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D016207:Cytokines; D004847:Epithelial Cells / Q000382:microbiology*; D005843:Geography; D016480:Helicobacter pylori / Q000737:chemistry*; D006801:Humans; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D015398:Signal Transduction; D013270:Stomach / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; C470179:AlpA protein, Helicobacter pylori; C119772:AlpB protein, Helicobacter pylori; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines