Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-8 expression through TAK-1/JNK/AP-1 pathways.

Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-8 expression through TAK-1/JNK/AP-1 pathways.
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猪繁殖与呼吸综合征病毒 (PRRSV) 通过 TAK-1JNKAP-1 途径上调 IL-8 表达

DOI:
10.1016/j.virol.2017.03.009
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发表时间:
2017-06
期刊:
影响因子:
3.7
通讯作者:
Feng WH
Feng WH
中科院分区:
医学3区
文献类型:
--
作者:
Liu Y;Du Y;Wang H;Du L;Feng WH

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猪生殖与呼吸综合征病毒(PRRSV)引起的呼吸窘迫急性期可能是肺部释放炎症细胞因子的结果。IL-8是主要的中性粒细胞趋化因子和激活因子,可能与PRRSV感染后的肺损伤有关。在这项研究中,我们表明,PRRSV诱导IL-8的表达在体内和体外。随后,我们证明JNK和NF-κB途径在PRRSV感染后被激活,并且是IL-8表达增强所必需的。我们进一步证实了PRRSV激活的TAK-1对JNK和NF-κB通路的激活以及IL-8的表达是必不可少的。此外,我们发现在克隆的猪IL-8(pIL-8)启动子中存在AP-1结合基序,该基序的缺失消除了pIL-8启动子的活性。最后,我们发现JNK激活的AP-1亚基c-Jun是PRRSV上调IL-8表达的关键。这些数据表明,PRRSV诱导的IL-8产生可能是通过TAK-1/JNK/AP-1途径。PRRSV感染诱导IL-8在体外和体内的表达。PRRSV通过TAK-1/JNK/AP-1途径上调IL-8表达。猪IL-8启动子中的AP-1元件是PRRSV诱导IL-8表达所必需的。
The acute phase of respiratory distress caused by porcine reproductive and respiratory syndrome virus (PRRSV) is likely a consequence of the release of inflammatory cytokines in the lung. IL-8, the main chemokine and activator of neutrophils, might be related to the lung injury upon PRRSV infection. In this study, we showed that PRRSV induced IL-8 expression in vivo and in vitro. Subsequently, we demonstrated that JNK and NF-κB pathways were activated upon PRRSV infection and required for the enhancement of IL-8 expression. We further verified that PRRSV-activated TAK-1 was essential for the activation of JNK and NF-κB pathways and IL-8 expression. Moreover, we revealed an AP-1 binding motif in the cloned porcine IL-8 (pIL-8) promoter, and deletion of this motif abolished the pIL-8 promoter activity. Finally, we found that the JNK-activated AP-1 subunit c-Jun was critical for the up-regulation of IL-8 expression by PRRSV. These data suggest that PRRSV-induced IL-8 production is likely through the TAK-1/JNK/AP-1 pathways. PRRSV infection induces IL-8 expression in vitro and in vivo. PRRSV up-regulates IL-8 expression through TAK-1/JNK/AP-1 pathways. AP-1 element in porcine IL-8 promoter is essential for PRRSV induced IL-8 expression.
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