Abstract
RANTES (regulated upon activation normal T cell expressed and secreted) is a chemoattractant cytokine important in the generation of inflammatory responses and human immunodeficiency virus resistance. In hematopoietic cells, RANTES is over-expressed by type I interferons (IFN-alpha and IFN-beta). The upstream region of the RANTES gene promoter contains a distal low affinity IFN-stimulated response element (ISRE). Specific mutagenesis in this ISRE-like motif abolished the activation of RANTES transcription by type I IFNs. Examination of the ISRE binding factors strongly suggested that signal transducer and activator of transcription (Stat)-2 and p48/IFN-stimulated gene factor 3gamma (ISGF3gamma) are not required for the induction of RANTES by type I IFNs. The specific requirement of Stat-1 was demonstrated using Stat-1-deficient U3A cells. These results revealed a non-classical ISRE/ISGF3 signal transduction pathway for the induction of RANTES by type I IFNs.
MeSH terms
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Base Sequence
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Cell Line
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Chemokine CCL5 / genetics*
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DNA / genetics
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DNA / metabolism
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Electrophoretic Mobility Shift Assay
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Humans
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Interferon Type I / pharmacology*
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Jurkat Cells
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Molecular Sequence Data
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Mutation / genetics
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Promoter Regions, Genetic / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Response Elements / genetics*
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STAT1 Transcription Factor
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STAT2 Transcription Factor
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Signal Transduction / drug effects*
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Trans-Activators / deficiency
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects*
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Up-Regulation / drug effects*
Substances
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Chemokine CCL5
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DNA-Binding Proteins
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IRF9 protein, human
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Interferon Type I
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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RNA, Messenger
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STAT1 Transcription Factor
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STAT1 protein, human
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STAT2 Transcription Factor
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STAT2 protein, human
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Trans-Activators
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Transcription Factors
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DNA