IFN-gamma-induced upregulation of Fcgamma-receptor-I during activation of monocytic cells requires the PKR and NFkappaB pathways

Molecular Immunology
K KårehedF Oberg

Abstract

Interferon (IFN)-gamma is a potent activator of macrophages, increasing the cells capacity to perform specific functions during inflammation and immune response. In this report we use IFN-gamma-induced upregulation of the high affinity receptor for IgG (FcgammaRI/CD64) in the human monocytic cell line U-937 as a model for monocytic activation. We show that upregulation of FcgammaRI is dependent on signals mediated by the dsRNA-dependent kinase PKR, and the transcription factor NFkappaB. Silencing of PKR expression by siRNA or inhibition of PKR by 2-aminopurine (2-AP) potently blocks the IFN-gamma-induced transcriptional activation of the FcgammaRI promoter. We find that the serine 727 phosphorylation of Stat1, required for full IFN-gamma-induced FcgammaRI promoter activity, is dependent on PKR. We further show that IFN-gamma induction of FcgammaRI upregulation is dependent on the NFkappaB pathway, as evidenced by inhibition of NFkappaB using a phosphorylation defective IkappaBalpha (S32A/S36A) mutant, or inhibiting the IkappaB-kinase (IKK) by treatment with BMS345541. Our results suggest that IFN-gamma-induced increase of FcgammaRI expression requires the integration of two signalling events: PKR-dependent Stat1 serine 727 phos...Continue Reading

References

Apr 25, 2000·The Journal of Biological Chemistry·S K RoyD V Kalvakolanu
Jun 13, 2000·Oncogene·T Decker, P Kovarik
Jul 19, 2000·The EMBO Journal·L B MaggiJ A Corbett
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·B R Williams
May 10, 2002·Nucleic Acids Research·Olivier Donzé, Didier Picard
Jan 4, 2003·Nature Reviews. Immunology·Siamon Gordon

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Citations

Jun 26, 2008·Nature Reviews. Immunology·Anthony J Sadler, Bryan R G Williams
Jan 22, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Britta DieselAlexandra K Kiemer
Feb 27, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M L ArnoldG A Böhmig
Mar 17, 2010·Journal of Cellular Physiology·William L BlalockLucio Cocco
Jul 28, 2013·Critical Care Medicine·Damien RouxJean-Damien Ricard
Jun 23, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cheng-Chieh TsaiChiou-Feng Lin
Dec 17, 2014·Journal of the American Chemical Society·Patrick J McEnaneyDavid A Spiegel

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