Tumour necrosis factor enhances induction by beta-interferon of a ubiquitin cross-reactive protein.
Tumour necrosis factor alpha (TNF-alpha) elicited an antiviral response in some cell lines (MG-63 and HEp-2) but not in others (MDBK). Cell lines that generated an antiviral response to TNF-alpha also showed induction of a 15K protein which shared sequence homology with ubiquitin and reacted with an antibody to ubiquitin. This ubiquitin cross-reactive protein (UCRP) had been demonstrated previously to be induced by interferon. The TNF-alpha induction of UCRP occurred at the level of transcription. TNF-alpha induction of both the antiviral state and the 15K protein was blocked by either monoclonal or polyclonal anti-beta-interferon (IFN-beta) antibody. However no measurable increase in the mRNA specific for IFN-beta was detected after TNF-alpha treatment. Nonetheless, in supernatants from cell cultures, the presence of an antiviral activity inhibitable by anti-IFN-beta antibody indicates that these cells are making IFN-beta already. We conclude that the TNF-alpha induction of antiviral activity and UCRP in cells is dependent upon the presence of constitutive low levels of IFN-beta in the responding cells. Furthermore TNF functions to enhance the existing IFN-beta activity.
Ahrens
P B
PB
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226.
Besançon
F
F
Mémet
S
S
Ankel
H
H
D003429:Cross Reactions; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004686:Encephalomyocarditis virus / Q000254:growth & development; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014452:Ubiquitins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D007370:Interferon Type I; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014452:Ubiquitins; D003513:Cycloheximide