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.
MeSH Terms
Blotting, Northern
Cells, Cultured
DNA/biosynthesis,genetics
DNA-Directed DNA Polymerase
Gene Amplification
Gene Expression Regulation
Humans
Interferon Type I/biosynthesis,genetics
Kinetics
Neutralization Tests
Oligonucleotides
RNA, Messenger/genetics
Tumor Necrosis Factor-alpha/physiology
Vesicular stomatitis Indiana virus/immunology
Chemicals
Interferon Type I
Oligonucleotides
RNA, Messenger
Tumor Necrosis Factor-alpha
DNA
DNA-Directed DNA Polymerase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jacobsen H
Institute of Virus Research, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Mestan J
Mittnacht S
Dieffenbach C W
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