Reference - Detail
| RRC ID | 42854 |
|---|---|
| Author | Lu H, Wu JY, Beswick EJ, Ohno T, Odenbreit S, Haas R, Reyes VE, Kita M, Graham DY, Yamaoka Y. |
| Title | Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains. |
| Journal | J Biol Chem |
| 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. |
| Volume | 282(9) |
| Pages | 6242-54 |
| Published | 2007-3-2 |
| DOI | 10.1074/jbc.M611178200 |
| PII | S0021-9258(20)52232-1 |
| PMID | 17202133 |
| PMC | PMC3130062 |
| MeSH | Adhesins, Bacterial / genetics Adhesins, Bacterial / physiology* Animals Bacterial Outer Membrane Proteins / genetics Bacterial Outer Membrane Proteins / physiology* Cell Line, Tumor Cytokines Epithelial Cells / microbiology* Geography Helicobacter pylori / chemistry* Humans Inflammation Mice Mice, Inbred C57BL Molecular Sequence Data Mutation Signal Transduction* Stomach / microbiology |
| IF | 4.238 |
| Times Cited | 46 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MKN28(RCB1000) MKN45(RCB1001) |