Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys
Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys
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DOI：
10.1038/80819
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发表时间：
2000-11-01
影响因子：
30.5
通讯作者：
Mantovani, A
中科院分区：
文献类型：
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作者：
D'Amico, G;Frascaroli, G;Mantovani, A
如最初对白细胞介素I（IL-1）II型受体所证明的，来自IL-1和肿瘤坏死因子家族的一些主要促炎细胞因子由在结构上不能进行信号传导的诱饵受体调节。在这里，我们报告说，伴随接触促炎信号和IL-10产生功能性诱饵受体的趋化因子系统。引起树突状细胞（DC）成熟和迁移到淋巴器官的炎症信号诱导趋化因子受体转换，伴随炎症受体（例如CCR 1、CCR 2、CCR 5）的下调和CCR 7的诱导。同时暴露于脂多糖（LPS）和IL-10阻断与DC成熟相关的趋化因子受体转换。LPS + IL-10处理的DC显示低表达CCR 7，高表达CCR 1、CCR 2和CCR 5。这些受体不能引起迁移。我们提供的证据表明，解偶联受体，表达在LPS + IL-10处理的细胞，隔离和抑制炎性趋化因子。对于暴露于活化信号和IL-10的单核细胞获得了类似的结果。因此，在炎性环境中，IL-10在DC和单核细胞上产生功能性诱饵受体，其充当炎性趋化因子的分子汇和清除剂。
As originally demonstrated for the interleukin I (IL-1) type II receptor, some primary proinflammatory cytokines from the IL-1 and tumor necrosis factor families are regulated by decoy receptors that are structurally incapable of signaling. Here we report that concomitant exposure to proinflammatory signals and IL-10 generates functional decoy receptors in the chemokine system. Inflammatory signals, which cause dendritic cell (DC) maturation and migration to lymphoid organs, induce a chemokine receptor switch, with down-regulation of inflammatory receptors (such as CCR1,CCR2, CCR5) and induction of CCR7. Concomitant exposure to lipopolysaccharide (LPS) and IL-10 blocks the chemokine receptor switch associated with DC maturation. LPS + IL-10-treated DCs showed low expression of CCR7 and high expression of CCR1, CCR2 and CCR5. These receptors were unable to elicit migration. We provide evidence that uncoupled receptors, expressed on LPS + IL-10-treated cells, sequester and scavenge inflammatory chemokines. Similar results were obtained for monocytes exposed to activating signals and IL-10. Thus, in an inflammatory environment, IL-10 generates functional decoy receptors on DC and monocytes, which act as molecular sinks and scavengers for inflammatory chemokines.