부산대학교 도서관

ABSTRACTHelicobacter pyloristrains that contain thecagpathogenicity island (PAI) elicit increased synthesis of gastric C-X-C chemokines, promote neutrophilic infiltration into the gastric epithelium, and stimulate the synthesis of interleukin-8 (IL-8) in cultured gastric epithelial cells. To investigate the effects ofcagPAI genes on the transcription of the IL-8 gene, the Kato-3 gastric epithelial cell line was stably transfected with plasmid DNA containing the IL-8 gene promoter fused to a luciferase reporter gene. The resulting reporter cell line, L5F11, was used to monitor the effects of infection in cell culture by H. pylori26695 and isogenic derivatives with null mutations in genes in thecagPAI on transcription of the IL-8 gene. We found that null mutations in eight open reading frames, including homologs of theAgrobacterium virB9, virB10, andvirB11genes, in the left half of the cagPAI abrogated the induction of IL-8 gene transcription. Further studies with the L5F11 cell line showed that IL-8 gene transcription induced byH. pyloriwas blocked by the protein tyrosine kinase inhibitor herbimycin A but not by the protein kinase C inhibitor calphostin C or by the protein kinase G inhibitor KT5823. IL-8 gene transcription in L5F11 cells could also be induced by the cytokine tumor necrosis factor alpha (TNF-α) without exposure to H. pylori. This TNF-α-induced IL-8 transcription was inhibited by the protein kinase A inhibitor H7, which had no significant effect onH. pylori-induced IL-8 transcription. These studies show that multiple genes in the left half of the cagPAI are essential for the transcription of the IL-8 gene in gastric epithelial cells and that this depends on protein tyrosine kinase activation.