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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
IL-10 expression is regulated by HPV E2 protein in cervical cancer cells
V H Bermúdez-Morales1, O Peralta-Zaragoza, J M Alcocer-González
1Division of Chronic Infections and Cancer, CISEI, National Institute of Public Heath, Morelos 62100, Mexico.
Abstract:
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.
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