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The ability of cells to resist the cytolytic actions of tumour necrosis factor (TNF) has been shown to require TNF-induced gene expression. It has been shown in some human cells that the gene encoding manganese superoxide dismutase (MnSOD), a TNF-induced gene, can provide resistance to TNF killing. Variation in the sensitivity to TNF was observed during subcloning of mouse SV40-transformed cell lines. This variation fell into three phenotypic classes. Cells were found that were either always resistant to TNF, always sensitive to TNF, and sensitive to TNF if inhibitors of transcription or translation were present. To determine if the regulation of MnSOD was responsible for the TNF sensitivity, Northern blot analysis was carried out. These experiments showed no correlation between expression and/or induction of the MnSOD mRNA and sensitivity or resistance to TNF. These data suggest that other pathways and gene products must therefore play a role for cells to resist TNF-mediated cellular lysis. |
