HELICOBACTER-PYLORI INFECTION ACTIVATES NF-KAPPA-B IN GASTRIC EPITHELIAL-CELLS

Background & Aims: Helicobacterpylori adheres to gastric epithelial ce lls and stimulates interleukin (IL)-8 production, This may be instrume ntal in neutrophil infiltration of the gastric epithelium that charact erizes H. pylori gastritis, This study examined the molecular mechanis ms leading to H. pylori-induced epithelial cell IL-8 production, Metho ds: Electrophoretic mobility shift analyses for NF-kappa B were perfor med on cell and nuclear extracts from H. pylori-infected AGS and Kato III human gastric epithelial cells. Results: H. pylori infection activ ated the transcription factor NF-kappa B and induced nuclear transloca tion of both NF-kappa B p50/p65 heterodimers and p50 homodimers, Nucle ar translocation of NF-kappa B (30 minutes) was followed by increased IL-8 messenger RNA (1 hour) and protein levels (4 hours) consistent wi th NF-kappa B up-regulation of IL-8 gene transcription, Pretreatment o f AGS cells with PDTC, which blocks NF-kappa B activation, inhibited H . pylori-induced increases in IL-8 production by 90%. Immunohistochemi cal studies using a monoclonal antibody that recognizes the I-kappa B binding region of p65 showed activated NF-kappa B in gastric epithelia l cells of patients with H. pylori gastritis, Conclusions: H. pylori i nfection activates NF-kappa B in gastric epithelial cells in vitro and in vivo. NF-kappa B is a transcriptional regulator of IL-8 production , and its activation after bacterial infection may be an important def ense response in gastrointestinal epithelial cells.