Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells
Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells
复制标题
DOI：
10.1096/fj.01-0245com
复制
发表时间：
2002-01-01
期刊：
影响因子：
4.8
通讯作者：
Bornstein, SR
中科院分区：
文献类型：
--
作者：
Galon, J;Franchimont, D;Bornstein, SR
糖皮质激素仍然是当今临床医学中使用的主要免疫调节剂。然而，它们作为抗炎和免疫抑制药物的作用是有益的和有害的。我们分析了糖皮质激素对健康供体外周血单个核细胞基因表达谱的影响。DNA微阵列分析结合定量TaqMan PCR和流式细胞术显示，糖皮质激素诱导的趋化因子，细胞因子和补体家族成员的表达，以及新发现的先天免疫相关基因，包括清道夫和Toll样受体。相反，糖皮质激素抑制适应性免疫相关基因的表达。糖皮质激素对炎症性T辅助细胞亚群和糖尿病相关基因簇同时具有抑制和刺激作用。在T细胞受体交联激活的细胞中，糖皮质激素下调了先前在静息细胞中上调的特定基因的表达，这表明它们发挥积极和消极作用的潜在新机制。考虑到糖皮质激素治疗的广泛和不断更新的兴趣，我们在这里描述的配置文件将是有用的，在设计更具体和有效的治疗策略。
Glucocorticoids continue to be the major immunomodulatory agents used in clinical medicine today. However, their actions as anti-inflammatory and immunosuppressive drugs are both beneficial and deleterious. We analyzed the effect of glucocorticoids on the gene expression profile of peripheral blood mononuclear cells from healthy donors. DNA microarray analysis combined with quantitative TaqMan PCR and flow cytometry revealed that glucocorticoids induced the expression of chemokine, cytokine, and complement family members as well as of newly discovered innate immune-related genes, including scavenger and Toll-like receptors. In contrast, glucocorticoids repressed the expression of adaptive immune-related genes. Simultaneous inhibitory and stimulatory effects of glucocorticoids were found on inflammatory T helper subsets and apoptosis-related gene clusters. In cells activated by T cell receptor cross-linking, glucocorticoids down-regulated the expression of specific genes that were previously up-regulated in resting cells, suggesting a potential new mechanism by which they exert positive and negative effects. Considering the broad and continuously renewed interest in glucocorticoid therapy, the profiles we describe here will be useful in designing more specific and efficient treatment strategies.