Tumour Necrosis Factor Enhances induction by beta-Interferon of a Ubiquitin Cross-reactive Protein

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Abstract
Tumour necrosis factor α (TNF-α) 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-α 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-α induction of UCRP occurred at the level of transcription. TNF-α induction of both the antiviral state and the 15K protein was blocked by either monoclonal or polyclonal anti-β-interferon (IFN-β) antibody. However no measurable increase in the mRNA specific for IFN-β was detected after TNF-α treatment. Nonetheless, in supernatants from cell cultures, the presence of an antiviral activity inhibitable by anti-IFN-β antibody indicates that these cells are making IFN-β already. We conclude that the TNF-α induction of antiviral activity and UCRP in cells is dependent upon the presence of constitutive low levels of IFN-β in the responding cells. Furthermore TNF functions to enhance the existing IFN-β activity.