The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha.
The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha.
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DOI：
10.1084/jem.186.7.1077
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发表时间：
1997-10-06
期刊：
影响因子：
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通讯作者：
Matsushima K
中科院分区：
文献类型：
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作者：
Khabar KS;Al-Zoghaibi F;Al-Ahdal MN;Murayama T;Dhalla M;Mukaida N;Taha M;Al-Sedairy ST;Siddiqui Y;Kessie G;Matsushima K
干扰素（IFN）在体外表现出强大的抗病毒活性，在病毒的早期防御中起着重要作用。像IFN一样，促炎趋化因子，白细胞介素(IL)-8，是由病毒诱导的，在病毒感染期间出现在循环中。在IFN的体外细胞病变效应实验中，我们发现IL-8可以以剂量依赖的方式抑制IFN-α活性。这种作用可被IL-8特异性单克隆抗体逆转。趋化因子能够减弱干扰素介导的病毒复制抑制，这是通过测量感染性病毒产量来确定的。IL-8也降低了IFN抑制病毒早期复制的能力，因为IL-8减弱了对病毒蛋白形成的抑制。IL-8似乎干扰了ifn介导途径的晚期而不是早期步骤，如早期基因表达。IL-8对IFN-α抗病毒活性的抑制作用与2 ',5 ' - a低聚腺苷酸合成酶活性的降低有关，这一途径与IFN-α抗脑心肌炎病毒的作用密切相关。了解拮抗IFN作用的途径可能会带来增强内源性和治疗性IFN的新方法。
Interferon (IFN) exhibits a potent antiviral activity in vitro and plays a major role in the early defense against viruses. Like IFN, the proinflammatory chemokine, interleukin (IL)-8, is induced by viruses and appears in circulation during viral infections. In an in vitro cytopathic effect assay for IFN, we found that IL-8 can inhibit IFN-α activity in a dose-dependent manner. This action was reversed by specific monoclonal antibodies to IL-8. The chemokine was able to attenuate the IFN-mediated inhibition of viral replication as determined by measuring infectious virus yield. IL-8 also diminished the ability of IFN to inhibit an early stage of viral replication since IL-8 attenuated the inhibition of the formation of viral proteins. It appeared that IL-8 interfered with a late rather than an early step of IFN-mediated pathway such as early gene expression. The IL-8 inhibitory action on IFN-α antiviral activity was associated with reduced 2′,5′-A oligoadenylate synthetase activity, a pathway well correlative with the anti– encephalomyocarditis virus action of IFN-α. Understanding pathways that antagonize IFN action may lead to novel approaches to potentiate endogenous and therapeutic IFN.