Ursolic acid promotes the release of macrophage migration inhibitory factor via ERK2 activation in resting mouse macrophages
Ursolic acid promotes the release of macrophage migration inhibitory factor via ERK2 activation in resting mouse macrophages
复制标题
DOI：
10.1016/j.bcp.2005.08.008
复制
发表时间：
2005-11-15
影响因子：
5.8
通讯作者：
Ohigashi, H
中科院分区：
文献类型：
--
作者：
Ikeda, Y;Murakami, A;Ohigashi, H
巨噬细胞移动抑制因子（Macrophage migration inhibitor factor，MIF）在天然免疫和炎症反应中起着重要作用.熊果酸（UA）是一种抗炎三萜羧酸，最近报道可诱导静息巨噬细胞（M phi）释放促炎介质。我们研究了UA对静息RAW264.7小鼠M phi中MIF蛋白释放的影响，发现UA以剂量和时间依赖性方式降低细胞内MIF蛋白水平并促进MIF释放到培养基中，而不影响mRNA水平。此外，三萜在30分钟内显著诱导促分裂原活化蛋白激酶激酶1/2（MEK 1/2）和细胞外信号调节激酶1/2（ERKI/2）的活化，而没有观察到p38 MAPK或INK蛋白的磷酸化。此外，UA促进的MIF释放被MEK 1/2抑制剂PD 98059显著抑制，而针对ERK 2的siRNA显著降低了MIF蛋白的释放量，但对ERK 1无影响。这些结果表明，UA通过激活ERK 2触发细胞内MIF蛋白的释放。(c)2005年爱思唯尔公司All rights reserved.
Macrophage migration inhibitory factor (MIF) plays some pivotal roles in innate immunity and inflammation. Ursolic acid (UA), an anti-inflammatory triterpene carboxylic acid, was recently reported to induce the release of pro-inflammatory mediators in resting macrophages (M phi). We investigated the effects of UA on MIF protein release in resting RAW264.7 mouse M phi, and found that it decreased intracellular MIF protein levels and promoted the release of MIF into the culture media in dose- and time-dependent manners, without affecting mRNA levels. Further, the triterpene strikingly induced activation of mitogen-activated protein kinase kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERKI/2) within 30 min, whereas no phosphorylation of p38 MAPK or INK protein was observed. In addition, UA-promoted MIF release was significantly inhibited by PD98059, a MEK1/2 inhibitor, while siRNA for ERK2, but not ERK1, significantly decreased the amount of MIF protein released. These results suggest that UA triggers the release of intracellular MIF protein through the ERK2 activation. (c) 2005 Elsevier Inc. All rights reserved.