Abstract
Interferon Regulatory Factor (IRF)-1 is a multifunctional transcription factor, involved in cell growth regulation, pathogen response and immune activation. To identify novel gene targets that may contribute to IRF-1 mediated activities, RNA fingerprinting was performed using NIH3T3 cells that inducibly express a hybrid form of IRF-1 under tetracycline regulated control. Secretory leukocyte protease inhibitor (SLPI) – a regulator of inflammation and an inhibitor of the LPS response – was identified as a gene repressed after doxycycline induced IRF-1 expression. Preliminary analysis of the human SLPI promoter identified an ISRE-like site located within the −221 to −200 region to which IRF-1 binds and a second, putative IRF-1 binding site upstream of the TATA box. Furthermore, co-transfection studies demonstrated that SLPI expression was inhibited by IRF-1 co-expression. The identification of SLPI as a target of IRF-1 regulation reveals a unique involvement of IRF-1 in repression of gene transcription and assigns a novel role for IRF-1 in inflammation.
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Acknowledgements
This work was supported by grants from the Medical Research Council of Canada and the Canadian Foundation for AIDS Research (CANFAR). H Nguyen is the recipient of an FCAR studentship, R Lin is the recipient of a Fraser, Monat, MacPherson Fellowship from McGill University and J Hiscott is the recipient of a Senior Scientist Award from the Medical Research Council of Canada.
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Nguyen, H., Teskey, L., Lin, R. et al. Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation. Oncogene 18, 5455–5463 (1999). https://doi.org/10.1038/sj.onc.1202924
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DOI: https://doi.org/10.1038/sj.onc.1202924
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