Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pylori infection.
BACKGROUND
Tumour necrosis factor (TNF) is a predominant cytokine produced in the gastric mucosa of patients with Helicobacter pylori infection. 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.


OBJECTIVE
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 pylori negative 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 in H pylori infected gastric mucosa. sTNF-Rs appear to protect gastric epithelial cells from TNF induced apoptosis in H pylori infection.
Shibata
J
J
Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Goto
H
H
Arisawa
T
T
Niwa
Y
Y
Hayakawa
T
T
Nakayama
A
A
Mori
N
N
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D046508:Culture Techniques; D053938:DNA Fragmentation; D005260:Female; D016481:Helicobacter Infections / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D012995:Solubility; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha