Regulation of the Human Interferon-Inducible 6-16 Promoter in Tumor Necrosis Factor-Sensitive and Resistant Mouse Cells: Role of cAMP as a Mediator of Signal Transduction

The human interferon (IFN)-inducible 6-16 gene is also induced by tumor necrosis factor (TNF) in human and mouse cells. A reporter gene carrying the IFN regulatory sequences of the human IFN-inducible 6-16 promoter linked to the bacterial chloramphenicol acetyltransferase gene was transfected into the adipocyte-differentiating fibroblast cell line TA1 and a TNF-resistant derivative (TA1 R-6). Both IFN and TNF induced the 6-16 reporter gene in TA1 cells. However, the induction of 6-16 by TNF was abolished by antibodies to IFNs-α/β. In the TNF-resistant derivative (TA1 R 6) TNF failed to induce the 6-16 plasmid construct. IFN, on the other hand, effectively induced the 6-16 promoter in TA1-R6. The block in activation of the 6-16 promoter in TNF-resistant cells can be reversed by the addition of compounds that increased the intracellular concentration of cAMP. These cAMP analogs induced IFN secretion in parental cells but not in the TA1-R6 cells.