Interferon-κ, a novel type I interferon expressed in human keratinocytes
Interferon-κ, a novel type I interferon expressed in human keratinocytes
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DOI：
10.1074/jbc.m102502200
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发表时间：
2001-10-26
影响因子：
4.8
通讯作者：
Moore, PA
中科院分区：
文献类型：
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作者：
LaFleur, DW;Nardelli, B;Moore, PA
高通量cDNA测序已经导致干扰素-κ的鉴定，干扰素-κ是I型干扰素的一个新的亚类，其与其他家族成员显示出类似于30%的同源性。干扰素-κ由207个氨基酸组成，包括27个氨基酸的信号肽和一系列在I型干扰素中保守的半胱氨酸。编码干扰素-κ的基因位于9号染色体的短臂上，邻近I型干扰素基因簇，并选择性地在表皮角质形成细胞中表达。在病毒感染后、暴露于双链RNA后或用干扰素-γ或干扰素-β治疗后，角质形成细胞中干扰素-κ的表达显著增强。干扰素-κ重组蛋白的给药以种属特异性方式赋予针对病毒感染的细胞保护。干扰素-κ激活干扰素刺激的反应元件信号传导途径和一组类似于由其他I型干扰素调节的基因，包括抗病毒介质和转录调节因子。中和I型干扰素受体的抗体完全阻断干扰素-κ信号传导，表明干扰素-κ利用与其他I型干扰素相同的受体。因此，干扰素-κ定义了I型干扰素的一个新的亚类，其在角质形成细胞中表达并扩展了介导宿主防御的已知蛋白质的库。
High throughput cDNA sequencing has led to the identification of interferon-kappa, a novel subclass of type I interferon that displays similar to 30% homology to other family members. Interferon-kappa consists of 207 amino acids, including a 27-amino acid signal peptide and a series of cysteines conserved in type I interferons. The gene encoding interferon-kappa is located on the short arm of chromosome 9 adjacent to the type I interferon gene cluster and is selectively expressed in epidermal keratinocytes. Expression of interferon-kappa is significantly enhanced in keratinocytes upon viral infection, upon exposure to double-stranded RNA, or upon treatment with either interferon-gamma or interferon-beta. Administration of interferon-kappa recombinant protein imparts cellular protection against viral infection in a species-specific manner. Interferon-kappa activates the interferon-stimulated response element signaling pathway and a panel of genes similar to those regulated by other type I interferons including anti-viral mediators and transcriptional regulators. An antibody that neutralizes the type I interferon receptor completely blocks interferon-kappa signaling, demonstrating that interferon-kappa utilizes the same receptor as other type I interferons. Interferon-kappa therefore defines a novel subclass of type I interferon that is expressed in keratinocytes and expands the repertoire of known proteins mediating host defense.