Expression of endogenous tumor necrosis factor as a protective protein against the cytotoxicity of exogenous tumor necrosis factor.

Based on the finding that expression of endogenous tumor necrosis factor (TNF) which is not detected in TNF-susceptible cells was observed in TNF-resistant cells, the assumption was made that endogenous TNF may be a protective protein against the cytotoxic activity of TNF. In order to confirm this possibility, we investigated the relationship between expression of endogenous TNF and TNF susceptibility by using the gene transfection method. When L-M, TNF-highly sensitive murine fibrosarcoma cells were transfected with a human TNF gene, the stable transfectants expressed endogenous TNF and acquired resistance to TNF. Conversely, when endogenous TNF synthesis was inhibited by introducing an antisense TNF gene into HeLa, TNF-less sensitive human cervical cancer cells, the sensitivity was enhanced. These findings indicate that endogenous TNF is one of the protective factors against the cytotoxic activity of TNF.