Ali Mehboob, Heyob Kathryn, Rogers Lynette K
Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
Sci Rep. 2016 Mar 4;6:22276. doi: 10.1038/srep22276.
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.
在暴露于母体脂多糖（LPS）和新生儿高氧环境的小鼠后代的肺部观察到持续性巨噬细胞。母体补充二十二碳六烯酸（DHA）可防止巨噬细胞积聚并改善肺发育。我们推测这些巨噬细胞与该模型中观察到的病理情况以及DHA补充的效果有关。从喂食标准饲料、对照饮食或补充DHA饮食的成年小鼠中分离出原代巨噬细胞。将巨噬细胞暴露于高氧（O2）环境24小时，再暴露于LPS环境6小时或24小时。我们的数据表明，在体内补充DHA后，Notch 1和Jagged 1蛋白水平显著降低，但在用标准饲料喂养并在体外补充DHA的小鼠分离出的巨噬细胞中未观察到类似结果。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B1和白三烯B4，而补充DHA可减弱这种释放。总体而言，我们的数据表明，如在体内观察到的那样，长期补充DHA会导致Notch 1/Jagged 1蛋白表达降低，然而，体外补充DHA足以抑制白三烯B4的释放并在共培养中保护上皮细胞。
