Transforming growth factor beta 1 (TGF-β1) modulates Epstein-Barr virus reactivation in absence of Helicobacter pylori infection in patients with gastric cancer

Cytokine. 2016 Jan:77:176-9. doi: 10.1016/j.cyto.2015.07.023. Epub 2015 Jul 31.

Abstract

Background: Transforming growth factor-beta 1 (TGF-β1), a multifunctional cytokine, acts as a key factor for Epstein-Barr virus (EBV) reactivation. We investigated the role of TGF-β1 in latent and lytic stages of EBV in relation to Helicobacter pylori infection among patients with gastric cancer (GC) and peptic ulcer disease (PUD).

Method: Gastric mucosal TGF-β1 expression was determined in 95 EBV positive patients with gastroduodenal pathology [GC 40, PUD 19 and non-ulcer dyspepsia (NUD) 36] by quantitative real time PCR. Presence of H. pylori infection was diagnosed when either culture or any two of three tests (RUT, histopathology and specific ureA PCR) were positive. Serum level of TGF-β1 was detected among 60 patients using ELISA.

Results: Mucosal TGF-β1 mRNA expression was detected in 85 of 95 EBV positive patients and it was significantly higher in patients with GC (p=0.042). TGF-β1 expression tended to be higher among H. pylori non-infected than infected patients (3.80±6.24 vs. 2.07±2.50, p=0.085). Both mRNA and serum level had significant association with lytic stage of EBV in absence of H. pylori infection when compared with its presence (5.21±4.00 vs. 2.29±2.89, p=0.040 and 842.00 [669.55] vs. 662.63 [628.76], p=0.049; respectively).

Conclusion: TGF-β1 expression was significantly associated with GC. TGF-β1 was higher both at expression and translational levels in lytic EBV infection without H. pylori suggests that H. pylori infection might play important role in preventing EBV reactivation through attenuated TGF-β1 expression. This might be a "wise host defense against EBV reactivation".

Keywords: Epstein-Barr virus; Gastric cancer; Helicobacter pylori; Transforming growth factor beta 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Enzyme-Linked Immunosorbent Assay
  • Epstein-Barr Virus Infections / genetics*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Helicobacter Infections / genetics
  • Helicobacter Infections / microbiology
  • Herpesvirus 4, Human / physiology
  • Host-Pathogen Interactions
  • Humans
  • Male
  • Middle Aged
  • Peptic Ulcer / genetics
  • Peptic Ulcer / virology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / virology
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / genetics*
  • Virus Activation / physiology

Substances

  • Transforming Growth Factor beta1