DEXAMETHASONE UP-REGULATES GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR EXPRESSION ON HUMAN MONOCYTES

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleu kin-3 (IL-3) are weak inducers of major histocompatibility complex (MH C) class II expression on purified human blood monocytes. The glucocor ticoid dexamethasone synergizes with GM-CSF or IL-3 for the upregulati on 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 mecha nism of dexamethasone action. We demonstrate that the capacity of dexa methasone to up-regulate GM-CSF-induced MHC class II expression correl ates with the capacity to up-regulate GM-CSF receptor, but not the int erferon-gamma (IFN-gamma) receptor, in a highly dose-dependent manner on monocytes. Although dexamethasone induces GM-CSF receptor expressio n, it does not confer responsiveness to IL-5, a cytokine that shares a common chain of its heterodimeric cytokine receptor signalling molecu le with IL-3 and GM-CSF. Three other steroid hormones, beta-oestradiol , vitamin D3 and dehydroepiandosterone (DHEA), were also tested for th eir capacity to up-regulate MHC class II expression All three mediator s failed to enhance MHC class II expression or GM-CSF receptor express ion on the surface of human monocytes. These experiments suggest that dexamethasone may act to upregulate GM-CSF-induced MHC class II antige n expression on monocytes by up-regulating cytokine receptor expressio n.