Docosahexaenoic acid-derived Oxidized Lipid Metabolites Modulate the Inflammatory Response of Lipolysaccharide-stimulated Macrophages

Publication date: Available online 12 May 2018 Source:Prostaglandins & Other Lipid Mediators Author(s): John P. Caron, Jeffrey C. Gandy, Jennifer L. Brown, Lorraine M. Sordillo Docosahexaenoic acid (DHA) supplementation has demonstrated beneficial effects in a number of inflammatory diseases. Increasingly, important contributions to its favorable effects are attributed downstream metabolites called docosanoids. Herein, we investigated the role of DHA-derived oxidized lipid metabolites on inflammatory mediator expression by RAW 264.7 murine macrophages. Specifically, macrophage incorporation of DHA, and the resultant biosynthesis of selected pro-resolving docosanoids was quantified. Docosanoid effects on the expression of selected pro-inflammatory cytokines in LPS-stimulated cultures was determined. Macrophages incorporated DHA in significant amounts. In the presence of DHA macrophages produced statistically significant amounts of several putative pro-resolving docosanoids compared to untreated controls. Among them, resolvins D1 and D2 and maresin 1 abrogated COX-2 and IL-1β gene expression in LPS-stimulated macrophages. In addition to these mediators, protectin DX inhibited LPS-stimulated macrophage expression of IL-6. Our results demonstrate that macrophages incorporate DHA in quantities sufficient for the biosynthesis of biologically-relevant concentrations of a number of pro-resolving docosanoids, certain of which modulate the inflammatory response of macrop...
Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research