ABSTRACT
Tumor necrosis factor (TNF) induces an antiviral state in various cell lines. This antiviral state is quite similar to that established by interferon (IFN), e.g., TNF treatment of HEp-2 cells induces 2',5'-oligoadenylate synthetase activity. Both antiviral activity and synthetase induction are greatly reduced when TNF treatment occurs in the presence of a beta interferon subtype 1 (IFN-beta 1)-neutralizing antiserum. However, no one has yet directly demonstrated IFN-beta 1 induction, either as an antiviral activity in supernatants from TNF-treated cells or as IFN-specific mRNA by Northern (RNA) blot analysis. We have adopted a recently described in vitro DNA amplification protocol for the detection of specific RNAs. By applying this method to RNA from HEp-2 cells, we could demonstrate increased levels of IFN-beta 1-specific transcripts after TNF treatment. Dose response and kinetics of IFN-beta 1 induction coincided with the TNF-induced antiviral state. Nuclear run-on analysis showed enhanced transcriptional activity of the IFN-beta 1 gene in TNF-treated cells. Our data substantiate a role of IFN-beta 1 as mediator of the biological activity of TNF in HEp-2 cells.
