Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes
Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes
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DOI：
10.1111/j.1365-2222.2004.01824.x
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发表时间：
2004-03-01
影响因子：
6.1
通讯作者：
Gutiérrez, C
中科院分区：
文献类型：
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作者：
Mozo, L;Suárez, A;Gutiérrez, C
背景 IL-10 在炎症反应中发挥免疫抑制作用。在接受糖皮质激素 (GC) 治疗的患者中检测到血浆 IL-10 水平升高，表明类固醇可能部分通过增加 IL-10 的产生来发挥其抑制作用。 目的 目的是确定类固醇上调 IL-10 产生的可能机制。为此，我们离体分析了GC对淋巴细胞和骨髓来源细胞组成型产生IL-10的影响。方法通过Percoll梯度分离单核细胞和T细胞，并通过玫瑰花结法纯化B细胞。分别通过 ELISA 和 Northern 印迹测定蛋白质和 mRNA IL-10 水平。 结果 在用生理剂量的地塞米松 (Dex) 预处理至少 12 小时后，单核细胞（而非 T 或 B 细胞）上调 IL-10 的组成型产生。 IL-10 的上调发生在蛋白质和 mRNA 水平，这可能表明 Dex 的作用是通过增加基因转录来实现的。其他类固醇也有类似的结果，它们的作用与剂量相关，与类固醇效力成正比，并被类固醇拮抗剂 RU486 完全逆转。因此，GC 可能通过 GC 受体与其 IL-10 启动子中的特定糖皮质激素反应元件序列结合来上调 IL-10 的转录水平。与单核细胞相比，分化的未成熟巨噬细胞和树突状细胞在用 Dex 预处理后并没有改变其组成型 IL-10 的产生。结论我们的结果支持以下事实：类固醇通过选择性触发单核细胞上的激活信号来上调组成型 IL-10 的产生。
Background IL-10 plays an immunosuppressive role in inflammatory responses. Increased plasma levels of IL-10 have been detected in patients under glucocorticoid (GC) therapy, indicating that steroids may exert their suppressive effect, in part, by increasing IL-10 production.Objectives The aim was to define possible mechanisms by which steroids up-regulate IL-10 production. To this end, we have analysed ex vivo the effect of GCs on the constitutive production of IL-10 by lymphocytes and cells of myeloid origin.Methods Monocytes and T cells were isolated by a Percoll gradient and B cells were purified by rosetting. Protein and mRNA IL-10 levels were determined by ELISA and by Northern blot, respectively.Results Monocytes, but not T or B cells, up-regulated the constitutive production of IL-10 following pre-treatment for at least 12 h with physiological doses of dexamethasone (Dex). Up-regulation of IL-10 occurred at both protein and mRNA levels, probably indicating that the effect of Dex was by incrementing gene transcription. Other steroids had similar outcomes, their effects being dose-related, proportional to the steroid potency and totally reversed by the steroid antagonist RU486. Thus, transcript levels of IL-10 were up-regulated by GCs probably through binding of the GC receptor to its specific glucocorticoid response element sequence in the IL-10 promoter. In contrast to monocytes, differentiated immature macrophages and dendritic cells did not vary their constitutive IL-10 production after pre-treatment with Dex.Conclusion Our results support the fact that steroids up-regulate constitutive IL-10 production by selectively triggering activation signals on monocytes.