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局部热疗可通过内源性干扰素依赖途径诱导尖锐湿疣中的抗病毒活性。

Local hyperthermia could induce antiviral activity by endogenous interferon-dependent pathway in condyloma acuminata.

机构信息

State Key Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang 110001, China.

出版信息

Antiviral Res. 2010 Nov;88(2):187-92. doi: 10.1016/j.antiviral.2010.08.012. Epub 2010 Aug 24.

Abstract

Local hyperthermia has been successfully used in the treatment of viral warts by mechanisms that have largely remained unclear. Using an organotypic culture system, we found that hyperthermia at 42 °C and 45 °C could induce a significant increase in the transcriptional expression of interferon (IFN)-α, IFN-β and IFN-γ, in a temperature-dependent manner in condyloma acuminata (CA), but not in normal skin. Accordingly, local hyperthermia could enhance the expression of 2'-5' oligoadenylate synthase and double-stranded RNA (dsRNA)-dependent protein kinase, two antiviral enzymes downstream of the IFN-dependant pathway. Hyperthermia led to an increase in IFN-α/β receptor transcripts, and an increase in the levels in phospho-Stat1 and phospho-Stat2 in CA, though it had no influence on the levels of Jak1, Tyk2, Stat1 and Stat2 transcriptional expression. Local hyperthermia was proved effective in treating human papillomavirus-infected skin. These results suggested that hyperthermia took effect partly by inducing the expression of local endogenous IFN and partly by subsequent IFN-induced antiviral activity via Jak-STATs signalling pathway in CA.

摘要

局部热疗已成功用于治疗病毒性疣,但其机制在很大程度上仍不清楚。我们使用器官型培养系统发现,在尖锐湿疣(CA)中,42°C 和 45°C 的热疗可呈温度依赖性诱导干扰素(IFN)-α、IFN-β 和 IFN-γ的转录表达显著增加,但在正常皮肤中则没有。因此,局部热疗可增强抗病毒酶 2'-5'寡聚腺苷酸合成酶和双链 RNA(dsRNA)依赖性蛋白激酶的表达,这两种酶是 IFN 依赖途径下游的两种抗病毒酶。热疗导致 CA 中 IFN-α/β 受体转录物增加,磷酸化 Stat1 和磷酸化 Stat2 水平增加,但对 Jak1、Tyk2、Stat1 和 Stat2 转录表达水平没有影响。局部热疗已被证明对治疗人乳头瘤病毒感染皮肤有效。这些结果表明,热疗的作用部分是通过诱导局部内源性 IFN 的表达,部分是通过 Jak-STATs 信号通路诱导 IFN 诱导的抗病毒活性来实现的。

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