title: Overexpression of Helicobacter pylori VacA N-terminal fragment induces proinflammatory cytokine expression and apoptosis in human monocytic cell line through activation of NF-κB.
abstract: Vacuolating cytotoxin (VacA) is an important virulence factor in the pathogenesis of Helicobacter pylori-related diseases. The aim of this study was to investigate the function of the amino-terminal 476 residue fragment (p52) of VacA and the possible molecular mechanisms responsible for its induction of proinflammatory cytokines secretion and apoptosis. Human acute monocytic leukemia cell line THP-1 was used as an in vitro model to study proinflammatory cytokines secretion and apoptosis induced by transfection of a recombinant plasmid encoding the amino-terminal 476 residue fragment (p52) of VacA. The results showed that VacA p52 overexpression induced the production of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nitric oxide, and reactive oxygen species in THP-1 cells in a time-dependent manner. VacA p52 overexpression also promoted THP-1 cells apoptosis. In addition, VacA p52 triggered the activation of nuclear factor kappa B (NF-κB), indicating a possible mechanism for its induction of proinflammatory cytokines secretion and cell apoptosis. Our study demonstrated that the induction of cytokines secretion and apoptosis by VacA p52 in THP-1 cells could be mediated through activation of nuclear factor kappa B.
authors.affiliation: Institute of Pathogenic Biology, University of South China, Hengyang 421001, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Luo
authors.forename: Cun-Yan
authors.initials: CY
authors.lastname: Li
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Yu
authors.forename: Shuang-Yang
authors.initials: SY
authors.lastname: Tang
authors.forename: Heng-Ling
authors.initials: HL
authors.lastname: Cai
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D016328:NF-kappa B; C074689:VacA protein, Helicobacter pylori