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. 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 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 mucose. sTNF-Rs appear to protect gastric epithelial cells from TNF induced apoptosis in H pylori infection.