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

Previous reports have shown that <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection is associated with respiratory diseases. However, the pathogenesis remains unclear. Vacuolating cytotoxin A (VacA) is a major <i>H. pylori</i> exotoxin. In this study, we investigated the signaling pathways involved in the inflammatory response to <i>H. pylori</i> infection and VacA. Mice were treated with <i>H. pylori</i> 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, <i>H. pylori</i> 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, <i>H. pylori</i> infection promoted VacA production. In an <i>in vitro</i> 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.