IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3
IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3
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DOI：
10.4049/jimmunol.178.8.4779
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发表时间：
2007-04-15
影响因子：
4.4
通讯作者：
Ziegler-Heitbrock, Loems
中科院分区：
文献类型：
--
作者：
Staples, Karl J.;Smallie, Timothy;Ziegler-Heitbrock, Loems
IL-10是一种重要的免疫抑制细胞因子，可以下调其他细胞因子的表达，并且已被证明可以下调自身。我们在这项研究中表明，用 IL-10 处理人单核细胞来源的巨噬细胞会以剂量和时间依赖性方式诱导 IL-10 mRNA，最佳诱导浓度为 100 ng/ml，6 小时，而 IL-10 诱导的 IL-10 蛋白可在 18 小时检测到。在同一细胞中，IL-10可以部分抑制LPS诱导的IL-10 mRNA，但只能降低到IL-10诱导的IL-10水平。由 -195 IL-10 启动子驱动的腺病毒荧光素酶报告基因构建体（包含 Stat 基序）很容易被 IL-10 和 LPS 诱导。该 Stat 基序的突变会消除该启动子的 IL-10 激活，但不会消除 LPS 激活。最后，我们表明显性失活 Stat3 蛋白的过度表达将阻止 IL-10 mRNA 的 IL-10 诱导，但不会阻止 LPS 诱导。这些数据表明，IL-10 通过激活转录因子 Stat3 以自分泌方式在单核细胞衍生的巨噬细胞中诱导 IL-10。
IL-10 is an important immunosuppressive cytokine that can down-regulate expression of other cytokines and has been shown to down-regulate itself. We show, in this study, that treatment of human monocyte-derived macrophages with IL-10 induces IL-10 mRNA in a dose- and time-dependent manner with an optimum induction at 100 ng/ml and at 6 h, whereas IL-10-induced IL-10 protein can be detected at 18 h. In the Same cells, IL-10 can partially suppress IL-10 mRNA induced by LPS, but only down to the level of IL-10-induced IL-10. An adenoviral luciferase reporter construct driven by the -195 IL-10 promoter, which contains a Stat motif, was readily induced by both IL-10 and LPS. Mutation of this Stat motif ablated IL-10 activation of this promoter, but not the LPS activation. Finally, we show that overexpression of a dominant-negative Stat3 protein will prevent IL-10 induction, but not LPS induction, of IL-10 mRNA. These data show that IL-10 induces IL-10 in monocyte-derived macrophages in an autocrine manner via activation of the transcription factor Stat3.