The synergistic cytocidal effect produced by immune interferon and tumor necrosis factor in HT-29 cells is associated with inhibition of rRNA processing and (2',5') oligo (A) activation of RNase L.

The cytocidal activity of human immune interferon (IFN-tau) in combination with recombinant tumor necrosis factor-alpha (TNF) was assessed in human colon carcinoma cell line HT-29. IFN-tau or TNF alone reduced cell viability by 15-20%, but in combination produced a synergistic cytotoxic effect which inhibited colony formation by 55-85%. TNF impaired the processing of ribosomal precursor 45S RNA to 32S RNA which resulted in the selective inhibition of 28S rRNA. Both TNF and IFN-tau induced the activity of (2',5') oligo (A) synthetase and produced selective degradation of 28S rRNA, effects possibly related to the (2',5') oligo (A)-dependent activation of RNase L. The combination of IFN-tau and TNF resulted in a marked reduction in the labeling of ribosomal precursor RNAs as well as mature rRNA. These results demonstrate that the posttranscriptional and processing effects of IFN-tau and TNF are related to the enhanced cytotoxicity by this combination of cytokines.