Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells.
Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells.
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DOI：
10.4049/jimmunol.160.5.2401
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发表时间：
1998-03
影响因子：
4.4
通讯作者：
Smita A. Sharma;M. Tummuru;M. Blaser;L. D. Kerr
中科院分区：
文献类型：
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作者：
Smita A. Sharma;M. Tummuru;M. Blaser;L. D. Kerr
在体内，胃部感染幽门螺杆菌会导致炎症细胞因子 IL-1、IL-6、TNF-α 和 IL-8 的大量产生。含有cag致病岛(cag+)并与溃疡和胃癌相关的幽门螺杆菌菌株比cag-菌株诱导更多的细胞因子产生。这些细胞因子的表达通常由转录因子复合物、核因子-κ B (NF-κ B) 通过其基因增强子/启动子区域中的 κ B 结合元件进行调节。我们报告，毒性更强的 cag+ 幽门螺杆菌菌株诱导 NF-kappa B-DNA 结合活性增加，从而提高 AGS 胃上皮细胞中 IL-8 的表达。 cag+ 幽门螺杆菌菌株可显着刺激 IL-8 启动子驱动的报告基因活性，而 cag- 菌株则不会。此外，cag 岛内特定基因（picA1 和 picB）的突变会消除增强的 NF-κ B 激活和 IL-8 转录。 IL-8 表达的增加受到 NF-κ B 或 NF-IL-6 结合元件突变的抑制。与cag-菌株相比，cag+菌株诱导含有RelA的NF-κB结合复合物的核定位增强，但NF-IL-6结合活性没有增加。这些研究表明，不同类型的幽门螺杆菌菌株激活 NF-κ B 的能力与其诱导 IL-8 转录的能力相关，并表明了在感染 cag+ 幽门螺杆菌菌株的受试者中观察到的炎症反应增强的机制。
In vivo, gastric infection with Helicobacter pylori leads to substantial production of the inflammatory cytokines IL-1, IL-6, TNF-alpha, and IL-8. H. pylori strains that contain the cag pathogenicity island (cag+) and are associated with ulceration and gastric carcinoma induce greater cytokine production than cag- strains. Expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kappa B (NF-kappa B) through kappa B-binding elements in the enhancer/promoter regions of their genes. We report that more virulent cag+ H. pylori strains induce increased NF-kappa B-DNA binding activity, which elevates IL-8 expression in AGS gastric epithelial cells. The cag+ H. pylori strains induce significant stimulation of IL-8 promoter-driven reporter activity, while cag- strains do not. Furthermore, mutation of specific genes within the cag island (picA1 and picB) ablates enhanced NF-kappa B activation and IL-8 transcription. Increased IL-8 expression is inhibited by mutation in either the NF-kappa B or NF-IL-6 binding element. The cag+ strains, compared with the cag- strains, induce enhanced nuclear localization of a RelA-containing NF-kappa B binding complex, but no increase in NF-IL-6 binding activity. These studies demonstrate that the ability of different types of H. pylori strains to activate NF-kappa B correlates with their ability to induce IL-8 transcription and indicate a mechanism for the heightened inflammatory response seen in subjects infected with cag+ H. pylori strains.