COMPARISON BETWEEN TUMOR-NECROSIS-FACTOR RESPONSE AND HEAT-SHOCK RESPONSE IN L929 CELLS - CELLULAR AND MOLECULAR ASPECTS

1. When L929 cells were treated with 10 mug/ml cycloheximide, 100 mug/ml puromycin, or 50 mM histidinol 2 h before and during heating at 43-degrees-C, these drugs afforded heat protection, i.e. an 8-fold increase in survival from 6 x 10(-2) to 4.5 x 10(-1) after 1.5 h at 43-degrees-C by treatment with 10 mug/ml cycloheximide. 2. In contrast, when cells were treated with the drug 2 h before and during rhTNF-alpha treatment, the drugs enhanced rhTNF cytotoxicity, i.e. an 8 to 36-fold decrease in survival from 9 x 10(-1) to 0.25-1.1 x 10(-1) after 13 h with 100 U/ml rhTNF-alpha. 3. In addition, an increase in manganous superoxide dismutase (MnSOD) mRNA was induced by 100 U/ml rhTNF-alpha alone or in combination with 100 mug/ml puromycin, but not by heat shock. Moreover, heat shock protein synthesis was induced by heating at 45.5-degrees-C for 10 min, but not by TNF. 4. These results show that the TNF response appears to be distinct from the heat shock response in L929 cells.