Phospholipid esters from herring roe promotes SPM biosynthesis in human monocyte-derived macrophages and a keratinocyte/fibroblast co-culture with implications for the treatment of psoriasis

Immune-mediated inflammatory disease (IMID) is a major public health issue which can affect a number of organs and tissues with a profound impact on quality of life and often present with comorbidities. Psoriasis is a chronic IMID affecting the skin which presents with both local and systemic inflammation as part of its pathophysiology. An oil rich in polar lipids extracted from the roe sacks of herring has been shown to have immunomodulatory functions and to improve the clinical symptoms and impact inflammatory cytokine pathways in psoriasis in a clinical trial. The lipidic nature of herring roe oil and its high content of marine polyunsaturated fatty acids could suggest 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 known involvement in the resolution of inflammation and return to homeostasis. We have therefore explored the influence of herring roe oil and phospholipid esters from herring roe on lipid mediator and SPM biosynthesis in IFN-γ and LPS-stimulated human monocyte-derived macrophages and an IL-17A-stimulated skin cell co-culture with keratinocytes and fibroblasts. Lipid mediators including SPMs were quantified from resulting 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 the macrophage cell supernatants also indicate activation of reparative pathways upon treatment with herring roe oil. In conclusion, we observed a 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 herring roe oil.