Interleukin-10 induces transcription of the early promoter of human papillomavirus type 16 (HPV16) through the 5′-segment of the upstream regulatory region (URR)
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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.
Copyright 2002 Elsevier Science BV.