NF-κB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein
NF-κB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein
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DOI：
10.1073/pnas.0409873102
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发表时间：
2005-06-28
影响因子：
11.1
通讯作者：
Backert, S
中科院分区：
文献类型：
--
作者：
Brandt, S;Kwok, T;Backert, S
幽门螺杆菌免疫显性蛋白 CagA 与严重胃炎和癌症有关。通过 IV 型分泌将 CagA 注射到胃上皮细胞中会导致肌动蛋白-细胞骨架重排和细胞分散。据报道，CagA 在转录因子 NF-κ B 和 IL-8 的诱导中没有作用，而转录因子 NF-κ B 和 IL-8 是慢性炎症的关键决定因素。在这里，我们提供了几条证据，表明 CagA 能够以时间和菌株依赖性方式诱导 IL-8。我们还表明，通过交换特定的 cagA 基因，高 IL-8 诱导菌株可以转化为低诱导菌株，反之亦然。我们的结果表明，CagA 诱导的 IL-8 释放通过 Ras -> Raf -> Mek -> Erk -> NF ->kappa B 信号通路以不依赖于 Shp-2 和 c-Met 的方式发生。因此，CagA 是一种多功能蛋白，能够影响肌动蛋白重塑和增强趋化因子释放。
The Helicobacter pylori immunodominant protein, CagA, is associated with severe gastritis and carcinoma. Injection of CagA into gastric epithelial cells by type IV secretion leads to actin-cytoskeletal rearrangements and cell scattering. CagA has been reported to have no role in the induction of transcription factor NF-kappa B and IL-8, which are crucial determinants for chronic inflammation. Here, we provide several lines of evidence showing that CagA is able to induce IL-8 in a time- and strain-dependent manner. We also show that by exchanging specific cagA genes, high IL-8-inducing H. pylori strains could be converted into low inducing strains and vice versa. Our results suggest that IL-8 release induced by CagA occurs via a Ras -> Raf -> Mek -> Erk -> NF ->kappa B signaling pathway in a Shp-2- and c-Met-independent manner. Thus, CagA is a multifunctional protein capable of effecting both actin remodeling and potentiation of chemokine release.