Inhibitor kappaB and nuclear factor kappaB in granulocyte-macrophage colony-stimulating factor antagonism of dexamethasone suppression of the macrophage response to Aspergillus fumigatus conidia

The Journal of Infectious Diseases
Jung-Hyun ChoiDavid A Stevens

Abstract

The dexamethasone (DEX) immunosuppressive effect on macrophage killing activity and cytokine production in response to Aspergillus fumigatus conidia is antagonized by granulocyte-macrophage colony-stimulating factor (GM-CSF). The molecular mechanism is unknown. We postulated that this antagonism is mediated by inhibitor kappaB (I kappaB) induction by DEX and is opposed by acceleration of I kappaB degradation by GM-CSF with or without conidia stimulation, with corresponding effects on translocation and activation of nuclear factor kappa B (NF-kappaB). We studied 2 types of cells, resident peritoneal macrophages from CD-1 mice and the murine macrophage RAW264.7 cell line. Cells were unstimulated or stimulated with conidia and simultaneously treated with DEX, GM-CSF, or DEX plus GM-CSF, for 2-4 hours. I kappaB degradation and NF-kappaB activation were assessed by Western blot. Macrophages stimulated with conidia alone increased NF-kappaB translocation. DEX increased I kappaB levels in cytoplasm and blocked translocation of NF-kappaB to the nucleus in unstimulated and conidia-stimulated macrophages. Conversely, GM-CSF decreased I kappaB levels. GM-CSF reversed the effect of DEX on I kappaB levels. NF-kappaB levels were minimal in D...Continue Reading

Citations

Apr 9, 2008·The Journal of Experimental Medicine·Jenna L CashDavid R Greaves
May 27, 2008·The Journal of Infectious Diseases·David A Stevens
Mar 28, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Amar Safdar
Mar 23, 2011·Infection and Immunity·Diana Diaz-ArevaloMarkus Kalkum
Dec 18, 2010·Future Microbiology·Louis Y A ChaiMihai G Netea
Oct 21, 2014·Current Treatment Options in Infectious Diseases·Anil A PanackalPeter R Williamson
May 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·E Jean CornishJames B Burritt
Sep 1, 2006·Medical Mycology·David A Stevens

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