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Interferon-ç induces cathepsin B expression in a human macrophage-like cell line by increasing both transcription and mRNA stability.

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We have demonstrated previously that treatment of the phorbol ester PMA-primed THP-1 human macrophage-like cells with interferon-ç (IFN-ç) in vitro induced time and dose-dependent increases in steady-state levels of cathepsin B (CB) mRNA. The present study was undertaken to investigate the mechanism of that increase. In vitro nuclear transcription (nuclear run-off) assays of CB gene expression were performed with purified nuclei from IFN-ç-treated or untreated THP-1 cells. These assays showed transcription to be increased approximately three-fold by IFN-ç in the PMA-primed THP-1 cells. Studies with á-amanitin indicated that the half-life of CB mRNA is prolonged after PMA and IFN-ç treatment, by more than 90%. Therefore, the elevated CB mRNA level results from a combination of IFN-ç-induced increase in the transcription rate of the CB gene and stabilization of the corresponding transcripts. The IFN-ç-mediated increase in CB gene transcription and steady-state mRNA level was blocked by á-amanitin or cycloheximide, suggesting the involvement of RNA polymerase II and the requirement of de novo protein synthesis.
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Document Type: Research Article

Affiliations: Medical Ovarian Cancer Section, Department of Developmental Therapeutics, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Publication date: August 1, 1998

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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