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 (IMID) 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 polyunsaturated fatty acids suggests involvement of lipid mediator pathways for the observed alleviation of psoriatic inflammation. Of particular interest is the super-family of lipid mediators termed specialized pro-resolving mediators (SPMs), due to their involvement in 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 LPS-stimulated human monocyte-derived macrophages and an IL-17A-stimulated keratinocyte/fibroblast co-culture. 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 RvE2 and RvE3 in both cell systems and upregulation of DHA-derived SPMs such as RvD2 and PDX. Observations of PCTR2 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 towards a protective and possibly reparative macrophage phenotype as well as promotion of biosynthesis of pro-resolving lipid mediators in a skin cell co-culture, thus demonstrating a possible mechanism for resolution of inflammation in the skin niche using HRO.