由Helicobacter pyloriCagA通过IKKββ的Src-cortactin依赖型氨酸酸化来增强ADP-肝素依赖的NF-κB激活
Irshad Sharafutdinov1, Nicole Tegtmeyer1, Barbara Friedrich1
1Department of Biology, Division of Microbiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.
杆菌通过CagA-cortactin-FAK-Src-IKKβ通路激活NF-κB和IL-8的分泌. 这项研究揭示了一种新的信号级联,有助于H. pylori诱导的炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- 激活B细胞的核因子卡帕-光链增强剂 (NF-κB) 对先天免疫非常重要.
- 杆菌利用皮质素进行介质素-8 (IL-8) 的分泌,这取决于NF-κB的激活.
- 在 H. pylori 诱导的 IL-8 释放中,皮质素的精确信号传递机制尚不清楚.
研究的目的:
- 阐明涉及H. pylori介导的NF-κB激活和IL-8分泌的特定皮质素信号通路.
- 为了研究皮质素,CagA,FAK,Src和TIFA在H. pylori感染期间NF-κB级联中的作用.
主要方法:
- 利用皮质素,FAK和TIFA淘汰细胞来评估NF-κB通路的激活.
- 感染了H. pylori的细胞,并用纯化的腺二酸盐 (ADP) -β-d-曼诺-肝素 (ADPH) 和CagA.
- 测量了IKKβ和p65NF-κB的酸化,以及IL-8的分泌.
主要成果:
- 皮质素淘汰细胞显示FAK和Src激活减少,减少IKKβ和p65酸化.
- 在野生类型细胞中,ADPH刺激的NF-κB激活和IL-8分泌被CagA增强.
- 在野生类型的细胞中观察到ADPH和CagA的联合作用,但在淘汰细胞中没有,突出显示了协同作用.
结论:
- 在H. pylori诱导的炎症反应中发现了一种新的CagA>皮质动脉>FAK>Src>IKKβ信号级联.
- 这一途径对于ADPH依赖的NF-κB激活和IL-8分泌至关重要.
- 通过这种新发现的级联,CagA增强了H. pylori介导的炎症信号传递.
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