Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains

Hong Lu, Yih Wu Jeng, Ellen J. Beswick, Tomoyuki Ohno, Stefan Odenbreit, Rainer Haas, Victor Reyes, Masakazu Kita, David Y. Graham, Yoshio Yamaoka

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53 Scopus citations

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/alpBdeleted mutants (ΔalpAB). 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-κB was exclusive to AlpAB from East Asian strains. ΔalpAB 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. pylorirelated clinical outcomes may relate to differential effects of East Asian and Western types of AlpAB on NF-ΔB-related proinflammatory signaling pathways.

Original languageEnglish (US)
Pages (from-to)6242-6254
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number9
DOIs
StatePublished - Mar 2 2007

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ASJC Scopus subject areas

  • Biochemistry

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