Biological activity of interleukins-28 and-29: Comparison with type I interferons
Biological activity of interleukins-28 and-29: Comparison with type I interferons
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DOI：
10.1016/j.cyto.2005.04.003
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发表时间：
2005-07-21
期刊：
影响因子：
3.8
通讯作者：
Wadhwa, M
中科院分区：
文献类型：
--
作者：
Meager, A;Visvalingam, K;Wadhwa, M
尽管与I型干扰素(IFN)的受体结合不同，但人IL-28A、IL-28B和IL-29(IL-28A、IL-28B和IL-29，分别命名为干扰素lambda-2{干扰素-lambda 2}、干扰素-lambda 3和干扰素-lambda 1，或统称为III型干扰素)是一个由三个结构相关的细胞因子组成的小家族，与干扰素一样，可诱导抗病毒活性。为了进一步研究IL-28A和IL-29的生物学特性，我们在一系列人类细胞系中比较了它们与干扰素的活性。我们发现，它们在更少的细胞系中诱导抗病毒活性，并且比IFN更弱；IL-28A的活性也低于IL-29。此外，我们发现IL-28A和IL-29诱导的报告基因--与荧光素酶相连的蛋白MxA启动子，或与分泌型碱性磷酸酶(SEAP)相连的干扰素刺激反应元件(ISRE)--比干扰素更弱。在大多数细胞系中，IFN均能诱导细胞增殖抑制，但只有人胶质母细胞瘤细胞系LN319表现出剂量依赖性的IL-29生长抑制作用。聚合酶链式反应定量IL-28/29受体亚基信使核糖核酸，IL-28Rα。和IL-10Rβ，表明它们的表达水平不同；虽然它们在有反应的LN319细胞系中的表达最高，但在相对无反应的细胞系中这两种mRNAs的表达较低但显著。综上所述，我们发现IL-28A和IL-29的作用类似于干扰素。但一般效果较差，在更有限的细胞系中具有活性。(C)2005爱思唯尔有限公司。保留所有权利。
Despite binding to receptors distinct from those of type I interferons (IFNs), human interleukins-28A, -28B and -29 (IL-28A, IL-28B and IL-29; alternatively named IFN lambda-2 {IFN-lambda 2}, IFN-lambda 3 and IFN-lambda 1, respectively, or collectively, type III IFNs), a small family of three structurally-related cytokines, are, like IFNs, known to induce antiviral activity. To further biologically characterize IL-28A and IL-29, we compared their activities with those of IFNs in a range of human cell lines. We found that they induced antiviral activity in fewer cell lines and more weakly than IFNs; also IL-28A was less active than IL-29. Additionally, we showed IL-28A and IL-29 induced reporter genes - protein MxA promoter linked to luciferase, or interferon stimulated response element (ISRE) linked to secreted alkaline phosphatase (SEAP) - more weakly than IFN. Antiproliferative activity was induced by IFNs in most cell lines, but only in one human glioblastoma cell line, LN319, was dose-dependent IL-29-growth inhibition demonstrable. Polymerase chain reaction (PCR) quantification of messenger (in) RNA of IL-28/29 receptor subunits, IL-28R alpha. and IL-10R beta, indicated variable expression levels;, although their expression was highest in the responsive LN319 cell line, lower but significant expression of both mRNAs was found in relatively unresponsive cell lines. In conclusion, we found IL-28A and IL-29 act similarly to IFNs. but are less effective generally and have activity in a more limited range of cell lines. (c) 2005 Elsevier Ltd. All rights reserved.