Interleukin-10 induces transcription of the early promoter of human papillomavirus type 16 (HPV16) through the 5′-segment of the upstream regulatory region (URR)
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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DOI：
10.1016/s0166-3542(02)00070-0
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发表时间：
2002-08-01
影响因子：
7.6
通讯作者：
Tyring, SK
中科院分区：
文献类型：
--
作者：
Arany, I;Grattendick, KG;Tyring, SK
各种促炎细胞因子对人乳头瘤病毒（HPV）转录的影响已得到证实。另一方面，抗炎细胞因子的作用尚未得到阐述，尽管事实上，白细胞介素-10（IL-10）的水平已被发现在宫颈发育不良或癌以及在宫颈的HIV阳性个体显着升高。这些病症也与病毒转录升高相关。因此，IL-10对HPV转录的影响可能在免疫活性或免疫抑制个体的宫颈病变的发病机制中是重要的。在本文中，我们描述了IL-10对HPV 16型转录的影响。我们发现用IL-10处理HPV 16阳性宫颈癌细胞在转录水平上增加了E7早期基因的mRNA水平。类似地，IL-10显著地且剂量依赖性地诱导报告系统中HPV早期启动子的转录。使用缺失突变体，我们确定该诱导定位于URR的5'区段。瞬时转染的反义STAT 3表达载体废除IL-10诱导的报告活性以及HPV 16 E7表达。这表明STAT 3直接结合URR并刺激转录或影响与5 '区结合的转录因子的表达和/或结合。我们的研究结果表明，在宫颈微环境中细胞因子表达改变的情况下（如发育不良进展、HIV感染），IL-10除了具有免疫抑制作用外，还可能增强HPV相关病变的持续性和进展。(C)2002 Elsevier Science B. V.保留所有权利。
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. (C) 2002 Elsevier Science B.V. All rights reserved.