Oxylipin profiling in endothelial cells in vitro – Effects of DHA and hydrocortisone upon an inflammatory challenge

• Published in: Prostaglandins & other lipid mediators Vol. 144; p. 106352
• Main Authors: Motta, A.C., Strassburg, K., Oranje, P., Vreeken, R.J., Jacobs, D.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Anti-Inflammatory Agents - pharmacology; Cell Line; Cytokines - metabolism; DHA; Docosahexaenoic Acids - pharmacology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Humans; Hydrocortisone; Hydrocortisone - pharmacology; Inflammation; Inflammation - metabolism; Inflammation - pathology; LC-LC/MS; Oxylipins; Oxylipins - metabolism; Resolution; Inflammation; LC-LC/MS; DHA; Hydrocortisone; Oxylipins; Resolution
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2019.106352

•Oxylipin profiles were measured in an in vitro model of endothelial inflammation.•TNFα/IL-1β triggered the COX pathway and the release of pro-inflammatory oxylipins.•DHA inhibited inflammatory pathways while turning on the pro-resolution program.•Hydrocortisone blunted the release of both inflammatory and resolution oxylipins. Omega-3 poly-unsaturated fatty acids have been shown to have beneficial effects on several inflammatory-driven endpoints such as cardiovascular diseases. The anti-inflammatory effects of docosahexaenoic acid (DHA) are largely mediated through various oxylipins. Yet, mechanistic insights are limited. Here, we measured 53 oxylipins using LC-MS/MS in an in vitro model of endothelial cell inflammation, and compared the changes induced by DHA to hydrocortisone, a well-established anti-inflammatory drug. DHA modified several oxylipins derived from different precursors such as DHA, AA, LA and EPA. In response to a TNFα and IL-1-β challenge, DHA clearly reduced many COX-derived pro-inflammatory oxylipins, yet to a minor extent when compared to hydrocortisone. DHA also upregulated metabolites from the CYP and LOX pathways as opposed to hydrocortisone. Thus, DHA reduced pro-inflammation and enhanced pro-resolution, while hydrocortisone blunted both the pro- and anti-inflammatory pathways. Our results may fuel further research on the mitigation of corticosteroids adverse side-effects.