Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU.1.
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.
Liu
Jianguo
J
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Ma
Xiaojing
X
D000818:Animals; D001483:Base Sequence; D018946:Chemokine CCL5 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1 / Q000502:physiology*; D050835:Interferon Regulatory Factors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1
D018946:Chemokine CCL5; D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1