Helicobacter pylori cytotoxin-associated gene A activates tumor necrosis factor-α and interleukin-6 in gastric epithelial cells through P300/CBP-associated factor-mediated nuclear factor-κB p65 acetylation

Helicobacter pylori-initiated chronic gastritis is characterized by the cytotoxin-associated gene (Cag) pathogenicity island-dependent upregulation of pro-inflammatory cytokines in gastric epithelial cells, which is largely mediated by the activation of nuclear factor (NF)-kappa B as a transcription factor. However, the precise regulation of NF-kappa B activation, particularly post-translational modifications in the CagA-induced inflammatory response, has remained elusive. The present study showed that Helicobacter pylori CagA, an important virulence factor, induced the expression of P300/CBP-associated factor (PCAF) in gastric epithelial cells. Further study revealed that PCAF was able to physically associate with the NF-kappa B p65 sub-unit and enhance its acetylation. More importantly, PCAF-induced p65 acetylation was shown to contribute to p65 phosphorylation and further upregulation of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in gastric adenocarcinoma cells. In conclusion, the results of the present study indicated that Helicobacter pylori CagA enhanced TNF-alpha and IL-6 in gastric adenocarcinoma cells through PCAF-mediated NF-kappa B p65 sub-unit acetylation.