Microalgae-derived oxylipins decrease inflammatory mediators by regulating the subcellular location of NF kappa B and PPAR-gamma

Oxylipins (OXLs) are bioactive molecules generated by the oxidation of fatty acids that promote the resolution of acute inflammation and prevent chronic inflammatory processes through molecular mechanisms that are not well known. We have previously reported the anti-inflammatory activity of microalgae-derived OXLs and OXL-containing biomass in two inflammatory bowel disease (IBD) models: 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis and TNBS-induced recurrent colitis. In this study, we examined the in vitro anti-inflammatory mechanism of action of the most abundant OXLs isolated from Chlamydomonas debaryana (13S-NOTE and 13S-HODE) and Nannochloropsis gaditana (15S-HEPE). These OXLs decreased IL-1 beta and IL-6 pro-inflammatory cytokines production as well as iNOS and COX-2 expression levels in THP-1 macrophages. In addition, OXLs decreased IL-8 production in HT-29 colon cells, the major chemokine produced by these cells. The interaction of OXLs with NF kappa B and PPAR-gamma signaling pathways was studied by confocal microscopy. In THP-1 macrophages and HT-29 colon cells, stimulated by LPS and TNF alpha respectively, a pre-treatment with 13S-NOTE, 13S-NODE and 15S-HEPE (100 mu M) resulted in a lower nuclear presence of NF kappa B in both cell lines. The study of the subcellular localization of PPAR-gamma showed that the treatment of THP-1 and HT-29 cells with these OXL5 caused the migration of PPAR-gamma into the nucleus. Colocalization analysis of both transcription factors in LPS-stimulated THP-1 macrophages showed that the pre-treatment with 13S-HOTE, 13S-HODE or 15S-HEPE lowered nuclear colocalization similar to control value, and increased cytosolic localization above control level. These results indicate that these OXLs could act as agonist of PPAR-gamma and consequently inhibit NF kappa B signaling pathway activation, thus lowering the production of inflammatory markers, highlighting the therapeutic potential of these OXLs in inflammatory diseases such as IBD. (C) 2017 Elsevier Ltd. All rights reserved.