title: Helicobacter pylori-mediated transcriptional regulation of the human beta-defensin 2 gene requires NF-kappaB.
abstract: Human beta-defensin 2 (hBD-2) is an antimicrobial peptide involved in host defence against bacterial infection in epithelial tissues. Its levels are dramatically increased after bacterial infection. The involvement of NF-kappaB in Helicobacter pylori-mediated induction of hBD-2 promoter activity was examined. A luciferase reporter plasmid containing the hBD-2 promoter extending from -2110 base pairs to -1 was transiently expressed in MKN45 cells, and promoter activity was determined after incubation with H. pylori for 6 h. Deletion or mutation of the NF-kappaB site at -208 abolished activation of the hBD-2 promoter. Only H. pylori strains carrying a cag pathogenicity island (PAI) induced activation of the NF-kappaB site of the hBD-2 promoter gene. By gel retardation analyses, H. pylori increased NF-kappaB binding to hBD-2 promoter gene sequences. Supershift analysis demonstrated that whereas H. pylori activated NF-kappaB p65-p65 and p50-p50 homodimers, and the p65-p50 heterodimer of NF-kappaB, only the p65-p65 homodimer bound to the NF-kappaB site of the hBD-2 promoter. Thus, specific NF-kappaB proteins are important cis-elements for induction of hBD-2 gene transcription by H. pylori.
authors.affiliation: Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Sakamoto, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Ogushi
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Hojo
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Kumatori
authors.forename: M
authors.initials: M
authors.lastname: Se
authors.forename: Y
authors.initials: Y
authors.lastname: Nakahara
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Moss
authors.forename: T
authors.initials: T
authors.lastname: Hirayama
mesh_terms: D002460:Cell Line; D005753:Gastric Mucosa / Q000382:microbiology*; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D023083:beta-Defensins / Q000235:genetics*
chemical_list: C106641:DEFB4A protein, human; D016328:NF-kappa B; D023083:beta-Defensins