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Antiviral Res. 2002 Aug;55(2):331-9.

Interleukin-10 induces transcription of the early promoter of human papillomavirus type 16 (HPV16) through the 5'-segment of the upstream regulatory region (URR).

Author information

1
Department of Microbiology/Immunology, The University of Texas Medical Branch, Galveston, TX 77555-1070, USA. aranyistvan@uams.edu

Abstract

The effects of various proinflammatory cytokines on the transcription of human papillomaviruses (HPVs) have been demonstrated. On the other hand, the role of anti-inflammatory cytokines has not been elaborated, despite the fact that levels of interleukin-10 (IL-10) have been found significantly elevated in cervical dysplasias or carcinomas as well as in the cervix of HIV-positive individuals. These conditions are also associated with elevated viral transcription. Thus, the impact of IL-10 on HPV transcription might be important in pathogenesis of cervical lesions in both immunocompetent or immunosuppressed individuals. In this paper we describe the effects of IL-10 on the transcription of HPV type 16. We found that treatment of HPV 16-positive cervical carcinoma cells with IL-10 increased mRNA levels of the E7 early gene at the level of transcription. Similarly, IL-10 significantly and dose-dependently induced the transcription from the HPV early promoter in a reporter system. Employing deletion mutants we determined that this induction is mapped to the 5' segment of the URR. Transient transfection of an antisense-STAT3-expression vector abolished IL-10-induced reporter activity as well as HPV 16 E7 expression. This suggests that STAT3 either directly binds to the URR and stimulates transcription or affects expression and/or binding of transcription factors that bind to the 5'-region. Our findings suggest a mechanism by which--in addition to its immunosuppressive effects--IL-10 might enhance persistence and progression of HPV-related lesions under conditions (e.g. dysplastic progression, HIV infection) when the cytokine expression in the cervical microenvironment changes.

PMID:
12103433
DOI:
10.1016/s0166-3542(02)00070-0
[Indexed for MEDLINE]

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