Reverse signaling through membrane-bound interleukin-15 (Retracted Article. See vol 286, pg 8708, 2011)
Reverse signaling through membrane-bound interleukin-15 (Retracted Article. See vol 286, pg 8708, 2011)
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DOI：
10.1074/jbc.m403182200
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Bulfone-Paus, S
中科院分区：
文献类型：
--
作者：
Budagian, V;Bulanova, E;Bulfone-Paus, S
这项研究的结果表明，在用可溶性 IL-15 受体-α 或抗 IL-15 抗体刺激后，膜锚定白细胞介素 (IL)-15 在 PC-3 人前列腺癌细胞和干扰素 γ 激活的人单核细胞的细胞表面上组成型表达，从而产生反向信号转导，介导涉及成员激活的从外到内的信号转导。 MAPK 家族（ERK 和 p38）和粘着斑激酶。膜结合的 IL-15 的存在不依赖于这些细胞的三聚体 IL-15 受体复合物的表达，并且抵抗酸性缓冲液或胰蛋白酶的处理。通过膜结合 IL-15 的反向信号传导显着增加了单核细胞产生的几种促炎细胞因子，例如 IL-6、IL-8 和肿瘤坏死因子-α，从而表明该过程与这些细胞的复杂免疫调节功能的相关性。此外，跨膜IL-15的刺激还增强了PC-3细胞系中IL-6和IL-8的转录，并促进PC-3细胞以及在细胞表面稳定表达IL-15的LNCaP人前列腺癌细胞的迁移。因此，IL-15可以作为一种具有生物活性的跨膜分子存在，具有双重配体-受体特性，具有诱导双向信号传导的潜力。这一事实凸显了 IL-15 生物学的复杂性达到了新的水平，并为我们理解这种多效性细胞因子调节的细胞反应提供了新的重要见解。
The results from this study implicate membrane-anchored interleukin (IL)-15 constitutively expressed on the cell surface of PC-3 human prostate carcinoma cells and interferon-gamma-activated human monocytes in reverse signaling upon stimulation with soluble IL-15 receptor-alpha or anti-IL-15 antibodies, mediating the outside-to-inside signal transduction that involves the activation of members of the MAPK family (ERK and p38) and focal adhesion kinase. The presence of membrane-bound IL-15 was not dependent on the expression of the trimeric IL-15 receptor complex by these cells and resisted treatment with acidic buffer or trypsin. Reverse signaling through membrane-bound IL-15 considerably increased the production of several pro-inflammatory cytokines by monocytes, such as IL-6, IL-8, and tumor necrosis factor-alpha, thereby indicating the relevance of this process to the complex immunomodulatory function of these cells. Furthermore, stimulation of transmembrane IL-15 also enhanced the transcription of IL-6 and IL-8 in the PC-3 cell line and promoted migration of PC-3 cells as well as LNCaP human prostate carcinoma cells stably expressing IL-15 on the cell surface. Thus, IL-15 can exist as a biologically active transmembrane molecule that possesses dual ligand-receptor qualities with a potential to induce bidirectional signaling. This fact highlights a new level of complexity in the biology of IL-15 and offers novel important insights into our understanding of the cellular responses modulated by this pleiotropic cytokine.