An Essential Role for STAT6-STAT1 Protein Signaling in Promoting Macrophage Cell-Cell Fusion
An Essential Role for STAT6-STAT1 Protein Signaling in Promoting Macrophage Cell-Cell Fusion
复制标题
DOI：
10.1074/jbc.m112.358226
复制
发表时间：
2012-09-21
影响因子：
4.8
通讯作者：
Miyamoto, Takeshi
中科院分区：
文献类型：
--
作者：
Miyamoto, Hiroya;Katsuyama, Eri;Miyamoto, Takeshi
巨噬细胞谱系细胞如破骨细胞和异物巨细胞（FBGCs）通过单核细胞的细胞-细胞融合形成多核细胞。最近，我们报道了两个7跨膜分子，破骨细胞刺激跨膜蛋白（OC-STAMP）和树突状细胞特异性跨膜蛋白（DC-STAMP），是体内和体外破骨细胞和FBGC细胞融合所必需的。然而，调控FBGC融合所需的信号在很大程度上仍然未知。在这里，我们发现巨噬细胞中信号换能器和转录激活因子1 （STAT1）的缺乏增强了细胞-细胞融合，并升高了FBGCs中DC-STAMP的表达。相反，在il -4诱导的FBGCs中，缺乏STAT6会增加STAT1的激活，显著抑制细胞-细胞融合，降低OC-STAMP和DC-STAMP的表达。此外，STAT1缺失或OC-STAMP/DC-STAMP的共表达都足以诱导无IL-4的FBGCs细胞-细胞融合。我们得出结论，STAT6-STAT1轴调节OC-STAMP和DC-STAMP的表达，并控制fbgc的融合机制。
Macrophage lineage cells such as osteoclasts and foreign body giant cells (FBGCs) form multinuclear cells by cell-cell fusion of mononuclear cells. Recently, we reported that two seven-transmembrane molecules, osteoclast stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP), were essential for osteoclast and FBGC cell-cell fusion in vivo and in vitro. However, signaling required to regulate FBGC fusion remained largely unknown. Here, we show that signal transducer and activator of transcription 1 (STAT1) deficiency in macrophages enhanced cell-cell fusion and elevated DC-STAMP expression in FBGCs. By contrast, lack of STAT6 increased STAT1 activation, significantly inhibiting cell-cell fusion and decreasing OC-STAMP and DC-STAMP expression in IL-4-induced FBGCs. Furthermore, either STAT1 loss or co-expression of OC-STAMP/DC-STAMP was sufficient to induce cell-cell fusion of FBGCs without IL-4. We conclude that the STAT6-STAT1 axis regulates OC-STAMP and DC-STAMP expression and governs fusogenic mechanisms in FBGCs.