Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains.
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.
Lu
Hong
H
Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA.
Wu
Jeng Yih
JY
Beswick
Ellen J
EJ
Ohno
Tomoyuki
T
Odenbreit
Stefan
S
Haas
Rainer
R
Reyes
Victor E
VE
Kita
Masakazu
M
Graham
David Y
DY
Yamaoka
Yoshio
Y
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
D018829:Adhesins, Bacterial; C470179:AlpA protein, Helicobacter pylori; C119772:AlpB protein, Helicobacter pylori; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines