Title: 889 Differential profiles of pro-inflammatory and specialized pro-resolving lipid mediators in PMA-treated skin biopsies from young and old donors
Abstract: The skin immune system is regulated by bioactive lipids that initiate and amplify inflammation but control its efficient ending also called resolution. When dysregulated, bioactive lipid mediators contribute to skin pathologies by unresolved inflammation leading sometimes to chronic inflammation or fibrosis. Recently, age-associated alterations in inflammation and resolution programs were reported in aged mice allowing us to hypothesize that inflammation and its resolution could be impaired in aged human skins. Using PMA-treated skin explants from young (24±9 yo) and old (58±3 yo) donors, we have performed a metabololipidomic study using LC/MS-MS. We have shown that prostaglandinE2 (PGE2), a pro-inflammatory mediator as well as the lipoxinA4 (LxA4), a pro-resolutive biomarker, were produced and temporally regulated in inflamed young skins. In contrast, a delayed and weaker inflammatory response with a seemingly defective production of specialized pro-resolving mediators was noticed in old skins. Using principal component analysis, we have also shown that in young skin arachidonic acid pathway was highly mobilized with subsequent biosynthesis of both pro-inflammatory mediators (PGE2, TXB2) and pro-resolving mediators (LxA4, LxB4). In old skins, the EPA/DHA pathways were rather mobilized without biosynthesis of final pro-resolving mediators. Hence, the metabololipidomic profiling of old skins uncovered an endogenous resolution program of inflammation that was associated with dysregulation and/or absence of pro-resolving mediators. Taken together, the present results seem to indicate a role for lipoxins to rebalance cutaneous inflammation during aging and to rescue failed resolution in aged skin.