title: 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.
authors.affiliation: Department of Gastroenterology, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Xintao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Guorong
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Gastroenterology, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Yehong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000107:Acetylation; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016366:Open Reading Frames; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D013270:Stomach / Q000166:cytology / Q000382:microbiology; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003603:Cytotoxins; D015850:Interleukin-6; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C508600:IL6 protein, human; C498143:RELA protein, human; C080866:cagA protein, Helicobacter pylori