NF-kappaB activation during acute Helicobacter pylori infection in mice.
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.
Ferrero
Richard L
RL
Uniteé de Pathogeénie Bacteérienne des Muqueuses, Institut Pasteur, 25-28 rue du Dr Roux, Paris 75724, France. Richard.Ferrero@med.monash.edu.au
Avé
Patrick
P
Ndiaye
Delphine
D
Bambou
Jean-Christophe
JC
Huerre
Michel R
MR
Philpott
Dana J
DJ
Mémet
Sylvie
S
D000818:Animals; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D017930:Genes, Reporter; D016481:Helicobacter Infections / Q000276:immunology*; D044922:Helicobacter felis / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D016328:NF-kappa B; D001616:beta-Galactosidase