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Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pyloriinfection
  1. J Shibataa,
  2. H Gotoa,
  3. T Arisawaa,
  4. Y Niwaa,
  5. T Hayakawaa,
  6. A Nakayamab,
  7. N Morib
  1. aSecond Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan, bDepartment of Pathology
  1. Dr J Shibata, Second Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466–8550, Japan.

Abstract

BACKGROUND Tumour necrosis factor (TNF) is a predominant cytokine produced in the gastric mucosa of patients with Helicobacter pyloriinfection. TNF induces apoptosis in a variety of cells. The soluble TNF receptors (sTNF-Rs) can be divided into sTNF-RI and sTNF-RII, both of which inhibit TNF activity. However, their precise mechanisms remain unclear.

AIM To investigate the role of sTNF-Rs in H pylori infection.

METHODS In 40 patients, production of TNF and sTNF-Rs in gastric mucosa was measured using biopsy specimens. In addition, in gastric epithelial cells, sTNF-R release in response to TNF and the protective effect of sTNF-Rs against the cytotoxic and apoptotic activities of TNF were examined.

RESULTS TNF and sTNF-R expression was significantly higher in H pylori positive than H pylorinegative patients. TNF dose-dependently induced sTNF-RI release from gastric epithelial cells. sTNF-RII was also released from the cells. TNF decreased cell viability, but the effect was very small. A combination of anti-sTNF-RI and anti-sTNF-RII monoclonal antibodies significantly increased TNF induced cytotoxicity and apoptosis of gastric epithelial cells.

CONCLUSIONS These results show that sTNF-Rs are actively produced inH pylori infected gastric mucosa. sTNF-Rs appear to protect gastric epithelial cells from TNF induced apoptosis in H pylori infection.

  • Helicobacter pylori
  • tumour necrosis factor
  • soluble TNF receptors
  • apoptosis
  • gastric mucosa
  • stomach
  • Abbreviations used in this paper

    TNF
    tumour necrosis factor
    sTNF-R
    soluble TNF receptor
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
    PCR
    polymerase chain reaction
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  • Abbreviations used in this paper

    TNF
    tumour necrosis factor
    sTNF-R
    soluble TNF receptor
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
    PCR
    polymerase chain reaction
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