The human papillomavirus type 18 (HPV-18) upstream regulatory region (URR) controls cell type-specific expression of the viral oncoproteins E6 and E7. The HPV-18 URR is active in the cervical carcinoma cell line HeLa but inactive in the hepatoma cell line HepG2. C/EBPss (NF-IL-6) was shown to participate as an important regulator in HPV transcription dependent on the cell type. The finding that C/EPBss is critical for HPV-18 URR activity and that C/EPBss is induced by IL-6 offers the opportunity of manipulating HPV activity by specific cytokine treatment. In this report, we show that treatment with IL-6 results in activation of HPV-18 URR activity in HepG2 cells. In contrast, the HPV-18 URR is not inducible by IL-6 in three cervical carcinoma cell lines. In all three cell lines we found decreased expression of the IL-6 receptor compared to the IL-6-responsive HepG2 cells, whereas the level of expression of the signal transduction component gp130 is present in all cells. These results suggest that cervical carcinoma cells may circumvent the IL-6-induced cellular defense mechanism through downregulation of the IL-6-receptor.
Copyright 1999 Academic Press.