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.
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