The Upregulation of TRAF1 Induced by Helicobacter pylori Plays an Antiapoptotic Effect on the Infected Cells.

Wan XK¹, Yuan SL¹, Tao HX¹, Diao LP¹, Wang YC¹, Cao C¹, Liu CJ¹.

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1State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.

Abstract

BACKGROUND:

Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a member of the TRAF family and is dysregulated in diseases, such as atheroma, lymphoma, and solid tumors, but the role of TRAF1 in gastric cancer remains unknown. This study was aimed to investigate the role of TRAF1 in Helicobacter pylori (H. pylori)-related cell apoptosis and gastric carcinogenesis.

MATERIALS AND METHODS:

The mRNA and protein expression levels of TRAF1 were measured in a panel of gastric cancer cell lines and in H. pylori -infected mice by quantitative real-time PCR (qPCR) and Western blotting. The transcription factor that mainly affects transcription of TRAF1 during H. pylori infection was identified. The roles of H. pylori virulence factors that regulate TRAF1 expression were analyzed using isogenic cagA-, vacA-, and cagE-null mutants. The effects of TRAF1 on gastric cell viability and apoptosis during H. pylori infection were detected using the standard MTS (cell viability) assay and flow cytometry, respectively.

RESULTS:

H. pylori infection induced TRAF1 overexpression in both gastric epithelial cells and mice. The expression of TRAF1 in response to H. pylori infection was majorly regulated by the activation of NF-κB and was strongly related to H. pylori virulence factor CagA. The upregulation of TRAF1 inhibited cell apoptosis and increased the viability of infected cells.

CONCLUSIONS:

H. pylori infection induces the overexpression of TRAF1 in gastric epithelial cells. The upregulation of TRAF1 plays an antiapoptotic role in H. pylori -infected gastric cells and may contribute to the gastric carcinogenesis.

KEYWORDS:

Helicobacter pylori ; CagA; NF-κB; TRAF1; apoptosis