Hawrylowicz C M, Guida L, Paleolog E
Department of Immunology, St Mary's Hospital Medical School, London, UK.
Immunology. 1994 Oct;83(2):274-80.
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.
粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-3（IL-3）是纯化的人血单核细胞上主要组织相容性复合体（MHC）II类表达的弱诱导剂。糖皮质激素地塞米松与GM-CSF或IL-3协同作用，可上调这些细胞上HLA-DR、-DP和-DQ抗原的mRNA及细胞表面表达。本研究的目的是探讨地塞米松的作用机制。我们证明，地塞米松上调GM-CSF诱导的MHC II类表达的能力与上调GM-CSF受体而非干扰素-γ（IFN-γ）受体的能力高度剂量依赖性地相关，且这种相关性存在于单核细胞上。虽然地塞米松可诱导GM-CSF受体表达，但它并未赋予细胞对IL-5的反应性，IL-5是一种与IL-3和GM-CSF共享其异二聚体细胞因子受体信号分子共同链的细胞因子。还测试了其他三种甾体激素，即β-雌二醇、维生素D3和脱氢表雄酮（DHEA）上调MHC II类表达的能力。所有这三种介质均未能增强人单核细胞表面的MHC II类表达或GM-CSF受体表达。这些实验表明，地塞米松可能通过上调细胞因子受体表达来上调GM-CSF诱导的单核细胞上MHC II类抗原的表达。
