Characterizing antiviral mechanism of interleukin-32 and a circulating soluble isoform in viral infection
Characterizing antiviral mechanism of interleukin-32 and a circulating soluble isoform in viral infection
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DOI：
10.1016/j.cyto.2011.12.024
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发表时间：
2012-04-01
期刊：
影响因子：
3.8
通讯作者：
Kim, Soohyun
中科院分区：
文献类型：
--
作者：
Bae, Suyoung;Kang, Dongjun;Kim, Soohyun
白细胞介素-32（IL-32）是一种炎性细胞因子，其活性与各种自身炎性疾病以及感染性病原体如结核分枝杆菌和病毒感染有关。然而，IL-32的确切抗病毒机制仍不清楚。我们检测了甲型H1N1流感患者血清中IL-32水平，IL-32水平显著升高。接下来，我们用水泡性口炎病毒（VSV）感染的WISH细胞检测了重组IL-32 γ（rIL-32 γ）的抗病毒活性，但没有观察到抗病毒活性。因此，我们研究了rIL-32处理的THP-1细胞的上清液，因为该细胞系有效地响应rIL-32 γ。rIL-32处理的THP-1细胞的上清液具有抗病毒作用，此外，激动性单克隆抗体进一步增强了rIL-32 γ的特异性抗病毒活性。THP-1细胞上清液的分级分离和质谱分析显示，rIL-32 γ的抗病毒活性是通过THP-1细胞产生的因子转铁蛋白，而不是rIL-32 γ对上皮细胞的直接作用。我们还表征了IL-32 γ转基因小鼠（TG）血清中分泌的可溶性IL-32 γ蛋白，但IL-32 α TG血清中没有。目前的结果表明，IL-32 γ的表达和其在个体中的遗传变异可能是病毒感染的一个重要方面。(C)2012爱思唯尔有限公司版权所有。
Interleukin-32 (IL-32) is an inflammatory cytokine, and its activity is associated with various auto-inflammatory disorders as well as infectious pathogens such as Mycobacterium tuberculosis, and viral infections. However, the precise antiviral mechanism of IL-32 remains unclear. We assessed the IL-32 level in the sera of H1N1 influenza A patients and IL-32 level was significantly elevated. Next we examined the antiviral activity of recombinant IL-32 gamma (rIL-32 gamma) with WISH cells infected by vesicular stomatitis virus (VSV) but no antiviral activity was observed. Therefore we investigated the supernatant of rIL-32-treated THP-1 cells since this cell line effectively responded to rIL-32 gamma. The supernatant of rIL-32-treated THP-1 cell possessed an antiviral effect and in addition, an agonistic monoclonal antibody further enhanced a specific antiviral activity of rIL-32 gamma. The fractionation and mass spectrometer analysis of the THP-1 cell supernatant revealed that the antiviral activity of rIL-32 gamma is via a THP-1 cell-produced factor, transferrin, rather than the direct effects of rIL-32 gamma on epithelial cells. We also characterized a secreted soluble IL-32 gamma protein in serum of IL-32 gamma transgenic mouse (TG), but not in that of IL-32 alpha TG. The present results suggest that IL-32 gamma expression and its genetic variation in individual could be an important aspect of viral infections. (C) 2012 Elsevier Ltd. All rights reserved.