Helicobacter pylori promotes inflammatory factor secretion and lung injury through VacA exotoxin-mediated activation of NF-κB signaling

Previous reports have shown that Helicobacter pylori (H. pylori) infection is associated with respiratory diseases. However, the pathogenesis remains unclear. Vacuolating cytotoxin A (VacA) is a major H. pylori exotoxin. In this study, we investigated the signaling pathways involved in the inflammatory response to H. pylori infection and VacA. Mice were treated with H. pylori and VacA, and histopathological analysis of lung tissues was performed using hematoxylin-eosin, Masson's trichrome, and periodic acid Schiff staining. The secretion of inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay. The expression of VacA, nuclear factor-kappa B (NF-κB), and p65 NF-κB was analyzed by Western blotting and immunofluorescence. Cell proliferation and apoptosis were assessed using the MTS assay and flow cytometry, respectively. In mice, H. pylori infection and VacA treatment promoted the secretion of the inflammatory factors interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), IL-6, and IL-8, increased p65 NF-κB protein phosphorylation, and induced lung injury. Furthermore, H. pylori infection promoted VacA production. In an in vitro cell model, VacA treatment significantly suppressed the proliferation of WI-38 and BEAS-2B cells, promoted apoptosis, induced TNF-α, IL-1β, IL-6, and IL-8 secretion, and promoted p65 NF-κB protein phosphorylation and NF-κB nuclear transfer. The NF-κB inhibitor BAY11-7082 alleviated VacA-induced inflammation and apoptosis and increased cell viability. In conclusion, VacA promotes the secretion of inflammatory factors and induces lung injury through NF-κB signaling.