DHA Suppresses Primary Macrophage Inflammatory Responses via Notch 1/ Jagged 1 Signaling.

Mehboob Ali,Kathryn Heyob,Lynette K Rogers

doi:10.1038/srep22276

Abstract

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.

Highlights

Macrophages accumulate in response to inflammation and facilitate host defense[11]
Oxidation was assessed by measuring glutathione (GSH), glutathione disulfide (GSSG), glutathione reductase (GR), and glutathione peroxidase (GPX) in primary macrophages treated with docosahexaenoic acid (DHA) in vivo and in vitro (Table 1)
While DHA supplementation substantially increased GSH contents in room air (RA, 21% O2)/phosphate buffered saline (PBS) treated macrophages compared to macrophages from controls, differences in other treatment groups were modest

Summary

Introduction

Macrophages accumulate in response to inflammation and facilitate host defense[11]. Previous reports have shown that bacterial infection as well as hyperoxia exposure can alter macrophage function in the lungs resulting in prolonged or aberrant release of injurious substances and propagation of further injury to adjacent lung cells[12,13]. We tested the hypothesis that DHA supplementation in vivo, using diets enriched in DHA, or in vitro, using direct DHA administration, would attenuate the effects of combined LPS and hyperoxia exposure on lung primary macrophages and immortalized MHS cells. To accomplish this we investigated the effects of DHA on antioxidant capacity, Notch expression, apoptosis, and the release of injurious mediators in co-cultured epithelial cells

Methods

Results

Conclusion