NF-κB Activation during AcuteHelicobacter pyloriInfection in Mice

Abstract

Nuclear factor κB (NF-κB) plays a key regulatory role in host cell responses toHelicobacter pyloriinfection in humans. Although mice are routinely used as a model to studyH. pyloripathogenesis, the role of NF-κB in murine cell responses to helicobacters has not been studied in detail. We thus investigated the abilities of differentHelicobacterisolates to induce NF-κB-dependent responses in murine gastric epithelial cells (GECs) and in transgenic mice harboring an NF-κB-responsivelacZreporter gene.H. pyloriandHelicobacter felisstrains up-regulated the synthesis in mouse GECs of the NF-κB-dependent chemokines KC (CXCL1) and MIP-2 (CXCL2). These responses werecagpathogenicity island (cagPAI) independent and could be abolished by pretreatment with a pharmacological inhibitor of NF-κB. Consistent with the in vitro data, experimentalHelicobacterinfection of transgenic mice resulted in increased numbers of GECs with nuclear β-galactosidase activity, which is indicative of specific NF-κB activation. The numbers of β-galactosidase-positive cells in mice were significantly increased at day 1 postinoculation with wild-typeH. pyloristrains harboring or not harboring a functionalcagPAI, compared to naive animals (P= 0.007 andP= 0.04, respectively). Strikingly, however, no differences were observed in the levels of gastric NF-κB activation at day 1 postinoculation withH. felisor at day 30 or 135 postinoculation withH. pylori. This work demonstrates for the first time the induction of NF-κB activation within gastric mucosal cells during acuteH. pyloriinfection. Furthermore, the data suggest that helicobacters may be able to regulate NF-κB signaling during chronic infection.