Nuclear Factor κB2 p52 Protein Has a Role in Antiviral Immunity through IκB Kinase ε-dependent Induction of Sp1 Protein and Interleukin 15
Nuclear Factor κB2 p52 Protein Has a Role in Antiviral Immunity through IκB Kinase ε-dependent Induction of Sp1 Protein and Interleukin 15
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DOI：
10.1074/jbc.m113.469122
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发表时间：
2013-08-30
影响因子：
4.8
通讯作者：
O'Neill, Luke A.
中科院分区：
文献类型：
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作者：
Doyle, Sarah L.;Shirey, Kari Ann;O'Neill, Luke A.
在这项研究中，我们描述了一个以前未报道的功能NF κ B2，NF κ B家族转录因子，在抗病毒免疫。NF κ B2在对病毒dsRNA的模拟物poly（I：C）的反应中被诱导。聚（I：C）通过TLR 3起作用，以需要I κ B激酶β（IKK β）的激酶活性和RelA/p65的反式激活潜力的方式诱导报道基因的p52依赖性反式激活。我们确定了一个新的NF κ B2结合位点的转录因子Sp1的启动子，这是必需的Sp1基因转录激活聚（I：C）。我们表明，Sp1是由poly（I：C）和呼吸道合胞病毒诱导IL-15所必需的，这种反应也需要NF κ B2和IKK κ B。我们的研究确定了NF κ B2作为IKK抑制剂在抗病毒免疫中的靶点，并首次描述了NF κ B2在病毒感染后基因表达调控中的作用。
In this study we describe a previously unreported function for NF kappa B2, an NF kappa B family transcription factor, in antiviral immunity. NF kappa B2 is induced in response to poly(I: C), a mimic of viral dsRNA. Poly(I: C), acting via TLR3, induces p52-dependent transactivation of a reporter gene in a manner that requires the kinase activity of I kappa B kinase epsilon (IKK epsilon) and the transactivating potential of RelA/p65. We identify a novel NF kappa B2 binding site in the promoter of the transcription factor Sp1 that is required for Sp1 gene transcription activated by poly(I: C). We show that Sp1 is required for IL-15 induction by both poly(I: C) and respiratory syncytial virus, a response that also requires NF kappa B2 and IKK epsilon. Our study identifies NF kappa B2 as a target for IKK epsilon in antiviral immunity and describes, for the first time, a role for NF kappa B2 in the regulation of gene expression in response to viral infection.