Herring roe PLs promote SPM biosynthesis in macrophages and a keratinocyte/fibroblast coculture as a model of psoriasis

Psoriasis is a chronic immune-mediated inflammatory disease affecting the skin, presenting with both local and systemic inflammation as part of its pathophysiology. An oil rich in phospholipids extracted from herring roe has been shown to have immunomodulatory properties and to improve clinical symptoms and impact inflammatory cytokine pathways in psoriasis in a clinical trial. The lipidic nature of herring roe oil (HRO) and its high content of PUFAs suggest the involvement of lipid mediator pathways for the observed alleviation of psoriatic inflammation. Of particular interest is the superfamily of lipid mediators termed specialized pro-resolving mediators (SPMs), due to their involvement in the resolution of inflammation and subsequent return to homeostasis. We therefore explored the influence of HRO and its phospholipids on lipid mediator and SPM biosynthesis in IFN-γ and lipopolysaccharide-stimulated human monocyte-derived macrophages and an IL-17A-stimulated keratinocyte/fibroblast coculture. Lipid mediators, including SPMs, were quantified from cell supernatants using a validated LC-MS/MS protocol. In these experiments, we observed broad SPM biosynthesis with dominant upregulation of resolvin E2 and resolvin E3 in both cell systems and upregulation of DHA-derived SPMs, such as resolvin D2 and protectin DX. Observations of protectin conjugate in tissue regeneration 2 in macrophage cell supernatants also indicate activation of reparative pathways upon treatment with HRO. In conclusion, we observed promotion of SPM biosynthesis associated with a shift toward a protective and possibly reparative macrophage phenotype as well as promotion of biosynthesis of proresolving lipid mediators in a skin cell coculture, thus demonstrating a possible mechanism for resolution of inflammation in the skin niche using HRO.