RRC ID |
42854
|
著者 |
Lu H, Wu JY, Beswick EJ, Ohno T, Odenbreit S, Haas R, Reyes VE, Kita M, Graham DY, Yamaoka Y.
|
タイトル |
Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains.
|
ジャーナル |
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.
|
巻・号 |
282(9)
|
ページ |
6242-54
|
公開日 |
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
|
引用数 |
46
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
MKN28(RCB1000)
MKN45(RCB1001) |