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Publication : Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU.1.

First Author  Liu J Year  2006
Journal  J Biol Chem Volume  281
Issue  28 Pages  19188-95
PubMed ID  16707500 Mgi Jnum  J:114864
Mgi Id  MGI:3690271 Doi  10.1074/jbc.M602059200
Citation  Liu J, et al. (2006) Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU.1. J Biol Chem 281(28):19188-95
abstractText  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-kappaB c-Rel and PU.1 via the NF-kappaB 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.
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