猪繁殖与呼吸综合征病毒通过JNK-AP-1 和 NF-B通路诱导IL-12 p40的产生
猪繁殖与呼吸综合征病毒通过JNK-AP-1 和 NF-B通路诱导IL-12 p40的产生
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DOI：
10.1016/j.virusres.2016.09.009
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发表时间：
2016
期刊：
影响因子：
5
通讯作者：
Wen-hai Feng
中科院分区：
文献类型：
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作者：
pathwaysZhibin Yu;Chen Huang;Qiong Zhang;Wen-hai Feng
猪繁殖与呼吸综合征病毒(PRRSV)主要感染单核/巨噬细胞，调节细胞因子的产生，调节宿主的免疫反应。IL-12p40是异源二聚体细胞因子IL-12的基本亚基，在细胞免疫应答中起关键作用。在本研究中，我们证明了PRRSV感染在体外和体内诱导了IL-12p40的产生，随后我们发现p38MAPK、JNK和NF-B的抑制剂显著降低了PRRSV诱导的IL-12p40的表达。为了进一步研究PRRSV感染诱导IL-12p40产生的分子机制，我们克隆并分析了猪IL-12p40启动子，其中发现了AP-1和NF-B基序。PRRSV感染后，JNK-AP-1和NF-B信号通路均被激活。综上所述，这些数据表明PRRSV通过JNK-AP-1和NF-B信号通路诱导IL-12p40的表达。我们的发现可能有助于我们理解PRRSV感染诱导IL-12产生的分子机制。
tPorcine reproductive and respiratory syndrome virus (PRRSV) mainly infects monocyte/macrophage cellsand modulates cytokine production to regulate host immune response. IL-12p40 is the basic subunit ofIL-12, a heterodimeric cytokine, which plays key roles in the cell-mediated immune response. In thepresent study, we demonstrated that PRRSV infection induced IL-12p40 production in vitro and in vivo.Subsequently, we showed that inhibitors of p38 MAPK, JNK, and NF-B dramatically reduced PRRSV-induced IL-12p40 expression. To further characterize the molecular mechanism of IL-12p40 productioninduced by PRRSV infection, we cloned and analyzed the porcine IL-12p40 promoter, in which AP-1 andNF-B motifs were found. In addition, both JNK-AP-1 and NF-B signaling pathways were activated byPRRSV infection. Taken together, these data indicate that PRRSV induces IL-12p40 expression through theJNK-AP-1 and NF-B signaling pathways. Our findings might facilitate our understanding of the molecularmechanisms of IL-12 production induced by PRRSV infection.