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• W2099115584 startingPage "1023" @default.
• W2099115584 abstract "BackgroundThe 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 κB (IκB) induction by DEX and is opposed by acceleration of IκB degradation by GM-CSF with or without conidia stimulation, with corresponding effects on translocation and activation of nuclear factor κB (NF-κB) MethodsWe 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. IκB degradation and NF-κB activation were assessed by Western blot ResultsMacrophages stimulated with conidia alone increased NF-κB translocation. DEX increased IκB levels in cytoplasm and blocked translocation of NF-κB to the nucleus in unstimulated and conidia-stimulated macrophages. Conversely, GM-CSF decreased IκB levels. GM-CSF reversed the effect of DEX on IκB levels. NF-κB levels were minimal in DEX-treated macrophage nuclear extracts, compared with those from GM-CSF–treated and GM-CSF plus DEX–treated macrophages ConclusionGM-CSF can reverse the DEX immunosuppressive effect by enhancing IκB degradation and promoting NF-κB translocation. This would allow macrophage production of proinflammatory cytokines, facilitating resistance to aspergillosis" @default.
• W2099115584 created "2016-06-24" @default.
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• W2099115584 date "2006-04-01" @default.
• W2099115584 modified "2023-09-24" @default.
• W2099115584 title "Inhibitor κB and Nuclear Factor κB in Granulocyte‐Macrophage Colony‐Stimulating Factor Antagonism of Dexamethasone Suppression of the Macrophage Response to<i>Aspergillus fumigatus</i>Conidia" @default.
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• W2099115584 doi "https://doi.org/10.1086/500948" @default.
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