Interferon-γ regulates apoptosis by releasing soluble tumor necrosis factor receptors in a gastric epithelial cell line

Background and Aims: Interferon (IFN)-γ and tumor necrosis factor (TNF) are predominant cytokines produced in the gastric mucosa of patients with Helicobacter pylori-infected gastritis. Several studies reported that IFN-γ and TNF induced the synergistic effect on many cell lines. We attempted to clarify the apoptotic activity and the synergistic effect of IFN-γ and TNF on the gastric epithelial cell, and whether IFN-γ relates to soluble TNF receptors (sTNF-R) release from the gastric epithelial cell. Methods: On the gastric epithelial cell line MKN45, cytotoxic and apoptotic effects of IFN-γ and TNF were examined. Next, sTNF-R released in response to IFN-γ and the protective effect of sTNF-R against the cytotoxic activity of TNF and IFN-γ were examined by blocking the release of sTNF-R with a serine protease inhibitor such as phenylmethylsulfonyl fluoride. Results: Interferon-γ significantly decreased cell viability, but TNF decreased it only slightly. Interferon-γ and TNF did not make a synergistic effect on cell viability and apoptosis. Interferon-γ and TNF induced sTNF-R release from gastric epithelial cells. Phenylmethylsulfonyl fluoride significantly inhibited shedding of sTNF-R and a synergistic effect of TNF and IFN-γ on apoptosis was observed. Conclusion: These results suggest that sTNF-R released by IFN-γ regulate the injury on the gastric epithelial cell line induced by TNF.