Beta interferon subtype 1 induction by tumor necrosis factor.
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.
Jacobsen
H
H
Institute of Virus Research, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Mestan
J
J
Mittnacht
S
S
Dieffenbach
C W
CW
D015152:Blotting, Northern; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004259:DNA-Directed DNA Polymerase; D005784:Gene Amplification; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D009500:Neutralization Tests; D009841:Oligonucleotides; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D007370:Interferon Type I; D009841:Oligonucleotides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D004259:DNA-Directed DNA Polymerase