Tumor Necrosis Factor Function Intracellularly against the Cytotoxicity of Exogenous Endogenous Tumor Necrosis Factor Exerts Its Protective

Based on the findings that expression of endogenous tumor necrosis factor (enTNF), which is not present in TNF-susceptible cells, was generally observed in TNF-resistant cells and that TNF gene transfection gives rise to TNF resistance, the assumption was made that enTNF may be a protective protein against the cytotoxicity of exogenous TNF. However, it remains unknown whether the protection by enTNF is exerted in an intracellular or extracellular (autocrine) manner. We therefore transfected a nonsecretory human TNF gene (pTNF A pro) into highly TNF-sensitive mouse tumorigenic fibroblasts (L-M cells) and investigated their TNF susceptibility. The transfectants expressed enTNF which was not secreted into the medium and acquired an appre ciable degree of resistance to exogenous TNF. A significant increase in the manganous Superoxide dismutase level was also noted in the trans fectants. These findings suggest that enTNF exerts its protective func tion intracellularly by inducing manganous Superoxide dismutase pro duction.