Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes
Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes
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DOI：
10.1182/blood-2006-02-001115
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发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Roth, Johannes
中科院分区：
文献类型：
--
作者：
Ehrchen, Jan;Steinmueller, Lars;Roth, Johannes
单核细胞和巨噬细胞可根据其激活状态促进或下调炎症反应。糖皮质激素（GCs）是目前应用最广泛的免疫抑制药物，其对单核细胞的作用尚不明确。通过微阵列技术分析气相色谱在人单核细胞中诱导的表达模式，我们首次发现了133个基因的气相色谱依赖性调控，包括腺苷A3受体、CD1d和IL-1受体II等抗炎分子。实时聚合酶链反应（PCR）和流式细胞术独立证实了结果。gc调控基因的功能聚类表明，它可以诱导单核细胞特性，如吞噬和运动，以及抑制粘附、细胞凋亡和氧化爆发。这些预测被独立的功能分析所证实。GCs上调fMLP受体，并特异性促进对该趋化剂的趋化性。此外，GCs促进炎症反应中抗炎单核细胞表型的存活，可能是通过抑制氧化应激引起的细胞凋亡。由于GCs具有诱导抗氧化特性和高吞噬促炎剂的能力，因此限制了组织损伤。因此，GC治疗并没有导致单核细胞效应功能的全面抑制，而是导致一种特定的抗炎表型的分化，这种表型似乎积极参与炎症反应的解决。
Monocytes and macrophages may either promote or down-regulate inflammatory reactions depending on their state of activation. The effects of glucocorticoids (GCs), the most widely used immunosuppressive drugs, on monocytes are currently not well defined. By analyzing the GC-induced expression pattern in human monocytes by microarray technology, we identified for the first time GC-dependent regulation of 133 genes, including anti-inflammatory molecules such as adenosine A3 receptor, CD1d, and IL-1 receptor II. The results were independently confirmed by real-time polymerase chain reaction (PCR) and flow cytometry. Functional clustering of GC-regulated genes indicated induction of monocytic properties such as phagocytosis and motility as well as repression of adhesion, apoptosis, and oxidative burst. These predictions were confirmed by independent functional assays. GCs up-regulate fMLP receptors and specifically promote chemotaxis to this chemoattractant. Furthermore, GCs promote survival of an anti-inflammatory monocytic phenotype in inflammatory reactions, probably by inhibition of apoptosis because of oxidative stress. GCs limit tissue damage because of induction of antioxidative properties and high capacity for phagocytosis of proinflammatory agents. Thus, GC treatment did not cause a global suppression of monocytic effector functions but results in differentiation of a specific anti-inflammatory phenotype which seems to be actively involved in resolution of inflammatory reactions.