Ferrero Richard L, Avé Patrick, Ndiaye Delphine, Bambou Jean-Christophe, Huerre Michel R, Philpott Dana J, Mémet Sylvie
Uniteé de Pathogeénie Bacteérienne des Muqueuses, Institut Pasteur, 25-28 rue du Dr Roux, Paris 75724, France.
Infect Immun. 2008 Feb;76(2):551-61. doi: 10.1128/IAI.01107-07. Epub 2007 Dec 10.
Nuclear factor kappaB (NF-kappaB) plays a key regulatory role in host cell responses to Helicobacter pylori infection in humans. Although mice are routinely used as a model to study H. pylori pathogenesis, the role of NF-kappaB in murine cell responses to helicobacters has not been studied in detail. We thus investigated the abilities of different Helicobacter isolates to induce NF-kappaB-dependent responses in murine gastric epithelial cells (GECs) and in transgenic mice harboring an NF-kappaB-responsive lacZ reporter gene. H. pylori and Helicobacter felis strains up-regulated the synthesis in mouse GECs of the NF-kappaB-dependent chemokines KC (CXCL1) and MIP-2 (CXCL2). These responses were cag pathogenicity island (cagPAI) independent and could be abolished by pretreatment with a pharmacological inhibitor of NF-kappaB. Consistent with the in vitro data, experimental Helicobacter infection of transgenic mice resulted in increased numbers of GECs with nuclear beta-galactosidase activity, which is indicative of specific NF-kappaB activation. The numbers of beta-galactosidase-positive cells in mice were significantly increased at day 1 postinoculation with wild-type H. pylori strains harboring or not harboring a functional cagPAI, compared to naive animals (P = 0.007 and P = 0.04, respectively). Strikingly, however, no differences were observed in the levels of gastric NF-kappaB activation at day 1 postinoculation with H. felis or at day 30 or 135 postinoculation with H. pylori. This work demonstrates for the first time the induction of NF-kappaB activation within gastric mucosal cells during acute H. pylori infection. Furthermore, the data suggest that helicobacters may be able to regulate NF-kappaB signaling during chronic infection.
核因子κB（NF-κB）在人体宿主细胞对幽门螺杆菌感染的反应中起关键调节作用。尽管小鼠常被用作研究幽门螺杆菌发病机制的模型，但NF-κB在鼠类细胞对螺杆菌反应中的作用尚未得到详细研究。因此，我们研究了不同幽门螺杆菌分离株在鼠胃上皮细胞（GECs）和携带NF-κB反应性lacZ报告基因的转基因小鼠中诱导NF-κB依赖性反应的能力。幽门螺杆菌和猫螺杆菌菌株上调了小鼠GECs中NF-κB依赖性趋化因子KC（CXCL1）和MIP-2（CXCL2）的合成。这些反应与空泡毒素致病岛（cagPAI）无关，并且可以通过用NF-κB的药理学抑制剂预处理来消除。与体外数据一致，转基因小鼠的实验性幽门螺杆菌感染导致具有核β-半乳糖苷酶活性的GECs数量增加，这表明NF-κB被特异性激活。与未感染的动物相比，接种携带或不携带功能性cagPAI的野生型幽门螺杆菌菌株后第1天，小鼠中β-半乳糖苷酶阳性细胞的数量显著增加（分别为P = 0.007和P = 0.04）。然而，引人注目的是，接种猫螺杆菌后第1天或接种幽门螺杆菌后第30天或135天，胃中NF-κB激活水平没有差异。这项工作首次证明了急性幽门螺杆菌感染期间胃黏膜细胞内NF-κB激活的诱导。此外，数据表明螺杆菌在慢性感染期间可能能够调节NF-κB信号传导。
