DHA Suppresses Primary Macrophage Inflammatory Responses via Notch 1/ Jagged 1 Signaling.
DHA Suppresses Primary Macrophage Inflammatory Responses via Notch 1/ Jagged 1 Signaling.
复制标题
DOI：
10.1038/srep22276
复制
发表时间：
2016-03-04
影响因子：
4.6
通讯作者：
Rogers LK
中科院分区：
文献类型：
--
作者：
Ali M;Heyob K;Rogers LK
在暴露于母体 LPS 和新生儿高氧的小鼠后代的肺部观察到持续存在的巨噬细胞。母体补充二十二碳六烯酸（DHA）可防止巨噬细胞的积累并改善肺部发育。我们假设这些巨噬细胞导致了该模型中观察到的病理状况以及 DHA 补充的影响。原代巨噬细胞是从喂食标准食物、对照饮食或添加 DHA 的饮食的成年小鼠中分离出来的。巨噬细胞暴露于高氧 (O2) 24 小时和 LPS 6 小时或 24 小时。我们的数据表明，体内补充 DHA 后，Notch 1 和 Jagged 1 蛋白水平显着减弱，但在体外喂养标准食物并补充 DHA 的小鼠中分离的巨噬细胞中，类似结果并不明显。活化的巨噬细胞与 MLE12 上皮细胞共培养导致上皮细胞释放高迁移率族蛋白 1 和白三烯 B4，并且通过补充 DHA 可以减弱这种释放。总的来说，我们的数据表明，体内观察到的长期补充 DHA 会导致 Notch 1/Jagged 1 蛋白表达下降，然而，体外补充 DHA 足以抑制 LTB4 的释放并保护共培养中的上皮细胞。
Persistent macrophages were observed in the lungs of murine offspring exposed to maternal LPS and neonatal hyperoxia. Maternal docosahexaenoic acid (DHA) supplementation prevented the accumulation of macrophages and improved lung development. We hypothesized that these macrophages are responsible for pathologies observed in this model and the effects of DHA supplementation. Primary macrophages were isolated from adult mice fed standard chow, control diets, or DHA supplemented diets. Macrophages were exposed to hyperoxia (O2) for 24 h and LPS for 6 h or 24 h. Our data demonstrate significant attenuation of Notch 1 and Jagged 1 protein levels in response to DHA supplementation in vivo but similar results were not evident in macrophages isolated from mice fed standard chow and supplemented with DHA in vitro. Co-culture of activated macrophages with MLE12 epithelial cells resulted in the release of high mobility group box 1 and leukotriene B4 from the epithelial cells and this release was attenuated by DHA supplementation. Collectively, our data indicate that long term supplementation with DHA as observed in vivo, resulted in deceased Notch 1/Jagged 1 protein expression however, DHA supplementation in vitro was sufficient to suppress release LTB4 and to protect epithelial cells in co-culture.