ENDOGENOUS TUMOR-NECROSIS-FACTOR EXERTS ITS PROTECTIVE FUNCTION INTRACELLULARLY AGAINST THE CYTOTOXICITY OF EXOGENOUS TUMOR-NECROSIS-FACTOR

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 DELTA 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 appreciable degree of resistance to exogenous TNF. A significant increase in the manganous superoxide dismutase level was also noted in the transfectants. These findings suggest that entnf exerts its protective function intracellularly by inducing manganous superoxide dismutase production.