N-arachidonoyl glycine induces macrophage apoptosis via GPR18
N-arachidonoyl glycine induces macrophage apoptosis via GPR18
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DOI：
10.1016/j.bbrc.2012.01.027
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发表时间：
2012-02-10
影响因子：
3.1
通讯作者：
Miyata, Atsuro
中科院分区：
文献类型：
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作者：
Takenouchi, Rina;Inoue, Kazuhiko;Miyata, Atsuro
N-花生四烯酰甘氨酸（NAGly）是脂氨基酸的一种，据报道其在实验性耳水肿或腹膜炎中表现出抗炎作用。然而，其基本机制迄今尚未阐明。在这项研究中，我们试图研究NAGly对巨噬细胞的影响，包括相关的信号通路。NAGly在小鼠巨噬细胞衍生的细胞系RAW264.7中有效诱导凋亡。用MEK和p38 MAPK抑制剂预处理可阻止NAGly诱导的细胞凋亡，但NAGly可激活ERK 1/2、p38 MAPK和JNK。此外，我们专注于GPR 18（孤儿G蛋白偶联受体之一）的含义，因为NAGly已被报道为GPR 18的候选配体。用百日咳毒素或siRNA敲低GPR 18的表达可显著减弱NAGly诱导的细胞凋亡。在小鼠腹腔巨噬细胞中，GPR 18 mRNA的表达在促炎刺激的巨噬细胞中升高，但在抗炎刺激的巨噬细胞中不升高;一致。与后者相比，NAGly显著降低前者的细胞活力。这些结果表明NAGly可能通过GPR 18参与巨噬细胞的功能。(C)2012 Elsevier Inc. All rights reserved.
N-arachidonoyl glycine (NAGly), a member of lipoamino acids, was reported to exhibit anti-inflammatory effects in experimental ear edema or peritonitis. However the underlying mechanisms have not been clarified so far. In this study, we attempt to investigate the effects of NAGly on macrophages, including the relevant signaling pathways. NAGly potently induced apoptosis in mouse macrophage-derived cell line, RAW264.7. Pretreatment with inhibitors for MEK and p38 MAPK prevented the apoptosis induced by NAGly, although NAGly activated ERK1/2, p38 MAPK and JNK. Further, we focused on implication of GPR18, one of the orphan G protein-coupled receptors, because NAGly has been reported as a candidate ligand for GPR18. Pretreatment with pertussis toxin or siRNA to knock down the expression of GPR18 significantly attenuated the apoptosis induced by NAGly. In mouse peritoneal macrophages, the expression of GPR18 mRNA was elevated in proinflammatory stimulated macrophages but not in anti-inflammatory stimulated macrophages; consistently. NAGly remarkably reduced cell viability of the former, as compared to the latter. These results suggest that NAGly might be involved in function of macrophages through GPR18. (C) 2012 Elsevier Inc. All rights reserved.