Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-κB, and PU.1
Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-κB, and PU.1
复制标题
DOI：
10.1074/jbc.m602059200
复制
发表时间：
2006-07-14
影响因子：
4.8
通讯作者：
Ma, Xiaojing
中科院分区：
文献类型：
--
作者：
Liu, Jianguo;Ma, Xiaojing
干扰素调节因子（IRF）-8是在干扰素-γ介导的信号传导和树突状细胞的发育和功能中重要的转录因子IRF家族的成员。受激活调节的正常T细胞表达和分泌（RANTES或CCL 5）是CC趋化因子蛋白家族的成员，是宿主防御感染因子和癌症中几种重要免疫细胞类型的强烈化学引诱物。在这里，我们报告说，RANTES表达在IRF-8无效的巨噬细胞刺激干扰素-γ和脂多糖显着下降。IRF-8可以与IRF-1协同激活RANTES基因转录。有趣的是，在体外和体内，IRF-8可以通过位于-88至-79的NF-κ B元件与NF-κ B c-Rel和PU. 1直接物理相互作用而独立于IRF-1激活RANTES转录。本研究揭示了IRF-8在调节RANTES基因表达中的新作用，以及IRF-8与其他几种重要转录因子相互作用以通过激活RANTES基因来启动针对致病性和炎症性挑战的先天免疫应答的潜在分子机制。
Interferon regulatory factor (IRF)-8 is a member of the IRF family of transcription factors important in interferon-gamma-mediated signaling and in the development and function of dendritic cells. Regulated on activation, normal T cell expressed and secreted (RANTES, or CCL5) is a member of the CC chemokine family of proteins, strongly chemoattractant for several important immune cell types in host defense against infectious agents and cancer. Here we report that RANTES expression in IRF-8-null macrophages stimulated with interferon-gamma and lipopolysaccharide is markedly decreased. IRF-8 can activate RANTES gene transcription in synergism with IRF-1. Interestingly, IRF-8 can activate RANTES transcription independently of IRF-1 through direct physical interactions with NF-kappa B c-Rel and PU.1 via the NF-kappa B element located at -88 to -79 in vitro and in vivo. This study uncovers a novel role of IRF-8 in the regulation of RANTES gene expression and the underlying molecular mechanisms whereby IRF-8 interacts with several other important transcription factors to initiate innate immune responses to pathogenic and inflammatory challenges by activating the RANTES gene.