It has been found that certain cytokines (IL-4, IL-10 and TGF-β1) are highly expressed locally in biopsies from patients with premalignant lesions and cervical cancer, and may induce a local immune-suppression state. In particular, IL-10 is highly expressed in tumor cells and its expression is directly proportional to the development of HPV-positive cervical cancer, suggesting an important role of HPV proteins in the expression of IL-10. In fact, we demonstrated that E6 and E7 HPV proteins regulate TGF-β1 gene expression in cervical cancer cells. Here, we found by band shifting analysis that the HPV E2 protein binds to the regulatory region of the human IL-10 gene (-2054 nt) and induces high promoter activity in epithelial cells. Additionally, cervical cancer cells transfected to express the HPV E2 protein induce elevated levels of IL-10 mRNA in human papillomavirus-infected cells. The elevated expression of IL-10 may allow for virus persistency, the transformation of cervical epithelial cells, and consequently cancer development.

Related Articles