Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains
Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains
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DOI：
10.1074/jbc.m611178200
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发表时间：
2007-03-02
影响因子：
4.8
通讯作者：
Yamaoka, Yoshio
中科院分区：
文献类型：
--
作者：
Lu, Hong;Wu, Jeng Yih;Yamaoka, Yoshio
幽门螺杆菌粘附于胃上皮细胞后，细胞内信号传导导致细胞因子的产生，从而导致H.幽门相关性胃损伤两个相邻的同源基因（alpA和alpB）编码H.幽门螺杆菌外膜蛋白，被认为与粘附和细胞因子诱导有关。我们将胃上皮细胞与野生型H. pylori菌株及其相应的alpA/alpB缺失突变体（Δ alpAB）。结果通过互补确认。流式细胞术证实AlpAB参与细胞粘附。alpAB的缺失减少胃上皮细胞中的白细胞介素（IL）-6诱导。alpAB的缺失减少了东亚菌株的IL-8诱导，但对西方菌株没有。所有检测的AlpAB阳性菌株均激活细胞外信号调节激酶、c-Fos和cAMP反应元件结合蛋白。Jun-N-末端激酶、c-Jun和NF-κ B的激活仅限于东亚菌株的AlpAB。Delta alpAB突变体在C57 BL/6小鼠的胃中定植较差，并且与较低的粘膜KC和IL-6水平相关。我们的研究结果表明，AlpAB可能通过介导粘附胃上皮细胞和调节促炎细胞内信号级联反应诱导胃损伤。已知的地理差异H。幽门螺杆菌相关的临床结果可能与东亚和西方类型的AlpAB对NF-κ B相关的促炎信号通路的不同作用有关。
Following adhesion of Helicobacterpylori 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 (Delta alpAB). 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-kappa B was exclusive to AlpAB from East Asian strains. Delta alpAB 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-kappa B-related proinflammatory signaling pathways.