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.

ABSTRACT

Helicobacter pylori­initiated chronic gastritis is characterized by the cytotoxin­associated gene (Cag) pathogenicity island­dependent upregulation of pro­inflammatory cytokines in gastric epithelial cells, which is largely mediated by the activation of nuclear factor (NF)­κB as a transcription factor. However, the precise regulation of NF­κB activation, particularly post­translational modifications in the CagA­induced inflammatory response, has remained elusive. The present study showed that Helicobacter pylori CagA, an important virulence factor, induced the expression of P300/CBP­associated factor (PCAF) in gastric epithelial cells. Further study revealed that PCAF was able to physically associate with the NF­κB p65 sub­unit and enhance its acetylation. More importantly, PCAF­induced p65 acetylation was shown to contribute to p65 phosphorylation and further upregulation of tumor necrosis factor (TNF)­α and interleukin (IL)­6 in gastric adenocarcinoma cells. In conclusion, the results of the present study indicated that Helicobacter pylori CagA enhanced TNF­α and IL­6 in gastric adenocarcinoma cells through PCAF­mediated NF­κB p65 sub­unit acetylation.