Department of Biochemistry and Molecular Biology, Anhui Medical University, 69 Meishan Road, Hefei, Anhui, 230032, China.
Mol Biol Rep. 2011 Jan;38(1):139-43. doi: 10.1007/s11033-010-0087-1. Epub 2010 Mar 23.
Interferons (IFNs) can activate the PI3K-AKT and Raf-MEK-ERK signal pathways and induce antiviral proteins (MxA, 2',5'-OAS and PKR) expression in specific cell lines. However, the relationship between those antiviral proteins expression and signal pathways remains unknown at present. Thus our experiments were designed to determine the exact relationship in HepG2.2.15 cell line. The results demonstrated that IFN-α and IL-29 were both able to activate PI3K-AKT and Raf-MEK-ERK signal pathways, and IFN-α up-regulated the expression of MxA, 2',5'-OAS and PKR whereas IL-29 increased mRNA expression of MxA and 2',5'-OAS and had no influence on PKR. Furthermore, MxA, 2',5'-OAS and PKR expression were down-regulated while PI3K-AKT signal pathway was blocked by LY294002. And MxA was up-regulated after Raf-MEK-ERK signal pathway being blocked by PD98059. These findings indicate that the expression of MxA, 2',5'-OAS and PKR are up-regulate by PI3K-AKT signal pathway, and Raf-MEK-ERK signal pathway has a negative regulatory effect on the expression of MxA and no significant effect on 2',5'-OAS and PKR.
干扰素(IFNs)可以激活 PI3K-AKT 和 Raf-MEK-ERK 信号通路,并在特定细胞系中诱导抗病毒蛋白(MxA、2',5'-OAS 和 PKR)的表达。然而,目前尚不清楚这些抗病毒蛋白表达与信号通路之间的关系。因此,我们的实验旨在确定 HepG2.2.15 细胞系中的确切关系。结果表明,IFN-α 和 IL-29 均可激活 PI3K-AKT 和 Raf-MEK-ERK 信号通路,IFN-α 上调 MxA、2',5'-OAS 和 PKR 的表达,而 IL-29 增加 MxA 和 2',5'-OAS 的 mRNA 表达,对 PKR 没有影响。此外,当 PI3K-AKT 信号通路被 LY294002 阻断时,MxA、2',5'-OAS 和 PKR 的表达下调,而当 Raf-MEK-ERK 信号通路被 PD98059 阻断时,MxA 上调。这些发现表明,MxA、2',5'-OAS 和 PKR 的表达受 PI3K-AKT 信号通路的上调调节,而 Raf-MEK-ERK 信号通路对 MxA 的表达具有负调节作用,对 2',5'-OAS 和 PKR 没有显著影响。