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 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)-κB as a transcription factor. However, the precise regulation of NF-κB 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-κB 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)-α and interleukin (IL).6 in gastric adenocarcinoma cells. In conclusion, the results of the present study indicated that Helicobacter pylori CagA enhanced TNF-α and IL.6 in gastric adenocarcinoma cells through PCAF.mediated NF-κB p65 sub.unit acetylation.