Sypniewski Daniel, Bednarek Ilona, Gałka Sabina, Loch Tomasz, Machnik Grzegorz
Department of Biotechnology and Genetic Engineering, Medical University of Silesia, Sosnowiec, Poland.
Acta Pol Pharm. 2008 May-Jun;65(3):345-51.
Interferon-alpha and ribavirin are currently the only drugs registered in the chronic hepatitis C therapy. Their actions are based on both direct antiviral activities, and their influence on genes expressions. In the presented study, using Jurkat cell line as an in vitro model for interferon-gamma synthesis, influence of interferon-alpha and ribavirin on the expressions of IFN-gamma and its receptor subunits (IFNgR1 and IFNgR2) were studied. Expressions of the studied genes were measured at the transcriptional level using Real-Time RT-PCR method. Results indicate that both drugs, IFN-alpha and ribavirin, induced changes in IFN-gamma and its receptor expressions. While IFN-alpha stimulated the expressions of the studied genes (IFN- gamma, IFNgR1, and IFNgR2), ribavirin showed the contradictory influence. The inhibitory effect of ribavirin dominated IFN-alpha action and was responsible for the decrease in the mRNA levels of IFN-gamma and the receptor of IFN-gamma. This phenomenon observed at in vitro model may be responsible for the IFN-gamma decrease during hepatitis C therapy with IFN-alpha and ribavirin which was suggested by some authors.
干扰素-α和利巴韦林是目前慢性丙型肝炎治疗中唯一注册的药物。它们的作用基于直接抗病毒活性以及对基因表达的影响。在本研究中，使用Jurkat细胞系作为干扰素-γ合成的体外模型，研究了干扰素-α和利巴韦林对IFN-γ及其受体亚基（IFNgR1和IFNgR2）表达的影响。使用实时逆转录聚合酶链反应（Real-Time RT-PCR）方法在转录水平测量所研究基因的表达。结果表明，干扰素-α和利巴韦林这两种药物均诱导了IFN-γ及其受体表达的变化。虽然干扰素-α刺激了所研究基因（IFN-γ、IFNgR1和IFNgR2）的表达，但利巴韦林显示出相反的影响。利巴韦林的抑制作用主导了干扰素-α的作用，并导致IFN-γ及其受体的mRNA水平下降。在体外模型中观察到的这种现象可能是一些作者所提出的在使用干扰素-α和利巴韦林治疗丙型肝炎期间IFN-γ降低的原因。
