Alternatively activated macrophages express the IL-27 receptor alpha chain WSX-1

Alternatively activated macrophages express the IL-27 receptor alpha chain WSX-1
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DOI:
10.1016/j.imbio.2006.05.008
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发表时间:
2006-01-01
期刊:
影响因子:
2.8
通讯作者:
Hoelscher, Christoph
Hoelscher, Christoph
中科院分区:
医学4区
文献类型:
--
作者:
Rueckerl, Dominik;Hessmann, Manuela;Hoelscher, Christoph

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白细胞介素(IL)-27受体-α WSX-1是异源二聚体IL-27受体的一种组分,在包括巨噬细胞在内的各种细胞类型上表达。我们先前证明IL-27诱导STAT-3并能够抑制活化的巨噬细胞中促炎细胞因子的产生,这表明IL-27可以调节过度炎症的新反馈机制。由于IL-4受体-α(IL-4 R α)诱导的交替激活的巨噬细胞也被描述为减弱病理性炎症免疫反应,我们分析了IL-27在交替巨噬细胞激活中的作用。在本研究中,与IL-10和IL-4一样,发现IL-27抑制活化的骨髓源性巨噬细胞中IL-12/23 p4 O的产生。尽管IL-10诱导巨噬细胞上IL-4 R α的上调,但受体表达不被IL 27触发。与IL-4相反,IL-27不诱导替代性巨噬细胞活化,但IL-4强烈上调巨噬细胞上WSX-1的表达,并且替代性巨噬细胞活化增强IL-27介导的信号传导。因此,我们从我们的研究中得出结论,IL-10、IL-4和IL-27通过在交替活化的巨噬细胞上连续上调IL-4 R α和WSX-1而协同调节巨噬细胞活化。(c)2006年Elsevier GmbH。All rights reserved.
The interleukin (IL)-27 receptor-alpha WSX-1 is one component of the heterodimeric IL-27 receptor that is expressed on various cell types including macrophages. We previously demonstrated that IL-27 induces STAT-3 and is able to inhibit the production of pro-inflammatory cytokines in activated macrophages suggesting a novel feed-back mechanism by which IL-27 can modulate excessive inflammation. Because IL-4 receptor-alpha (IL-4R alpha)-induced alternatively activated macrophages have also been described to attenuate pathological inflammatory immune responses, we analyzed the contribution of IL-27 in alternative macrophage activation. In the present study, like IL-10 and IL-4, IL-27 was found to suppress IL-12/23p4O production in activated bone marrow-derived macrophages. Whereas IL-10 induced the upregulation of the IL-4R alpha on macrophages, receptor expression was not triggered by IL27. In contrast to IL-4, IL-27 did not induce alternative macrophage activation but IL-4 strongly upregulated the expression of WSX-1 on macrophages and alternative macrophage activation enhanced IL-27-mediated signalling. We therefore conclude from our study that IL-10, IL-4 and IL-27 collaborate in modulating macrophage activation by successive upregulation of the IL-4R alpha and WSX-1 on alternatively activated macrophages. (c) 2006 Elsevier GmbH. All rights reserved.