Soluble interleukin-6 receptor activates the human papillomavirus type 18 long control region in SW756 cervical carcinoma cells in a STAT3-dependent manner

Cervical carcinoma cells producing high levels of interleukin-6 (IL-6) were shown to be unresponsive to the cytokine IL-6 due to the loss of their IL- 6 receptor. Addition of IL-6 receptor in a soluble form restores IL-6 signa lling in SW756 carcinoma cells. This leads to a rapid and strong activation of the transcription factor signal transducer and activator of transcripti on 3 (STAT3). Nuclear factor IL-6 (NF-IL6, C/EBP beta) was induced only as a late event. While C/EBP beta significantly repressed the human papillomav irus type 18 long control region (HPV18-LCR), IL-6 signalling unexpectedly activated the HPV18-LCR in these cells. This IL-6 receptor-mediated inducti on could be completely reverted by transfection of a dominant-negative STAT 3 but not STAT1 expression construct, indicating that STAT3 might play an i mportant role in HPV18 oncogene promoter activation.