Dexamethasone up-regulates granulocyte-macrophage colony-stimulating factor receptor expression on human monocytes.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are weak inducers of major histocompatibility complex (MHC) class II expression on purified human blood monocytes. The glucocorticoid dexamethasone synergizes with GM-CSF or IL-3 for the upregulation of HLA-DR, -DP and -DQ antigen mRNA and cell-surface expression by these cells. The purpose of the present study was to address the mechanism of dexamethasone action. We demonstrate that the capacity of dexamethasone to up-regulate GM-CSF-induced MHC class II expression correlates with the capacity to up-regulate GM-CSF receptor, but not the interferon-gamma (IFN-gamma) receptor, in a highly dose-dependent manner on monocytes. Although dexamethasone induces GM-CSF receptor expression, it does not confer responsiveness to IL-5, a cytokine that shares a common chain of its heterodimeric cytokine receptor signalling molecule with IL-3 and GM-CSF. Three other steroid hormones, beta-oestradiol, vitamin D3 and dehydroepiandosterone (DHEA), were also tested for their capacity to up-regulate MHC class II expression. All three mediators failed to enhance MHC class II expression or GM-CSF receptor expression on the surface of human monocytes. These experiments suggest that dexamethasone may act to up-regulate GM-CSF-induced MHC class II antigen expression on monocytes by up-regulating cytokine receptor expression.
Department of Immunology, St Mary's Hospital Medical School, London, UK.
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Hawrylowicz
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Guida
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Paleolog
D000328:Adult; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000187:drug effects*; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D006681:HLA-D Antigens; D015848:Interleukin-5; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D017471:Receptors, Interferon; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor