Distribution of Bioactive Lipid Mediators in Human Skin

Abstract

The skin produces bioactive lipids that participate in physiological and pathological states, including homeostasis, induction, propagation, and resolution of inflammation. However, comprehension of the cutaneous lipid complement, and contribution to differing roles of the epidermal and dermal compartments, remains incomplete. We assessed the profiles of eicosanoids, endocannabinoids, N-acyl ethanolamides, and sphingolipids, in human dermis, epidermis, and suction blister fluid. We identified 18 prostanoids, 12 hydroxy-fatty acids, 9 endocannabinoids and N-acyl ethanolamides, and 21 non-hydroxylated ceramides and sphingoid bases, several demonstrating significantly different expression in the tissues assayed. The array of dermal and epidermal fatty acids was reflected in the lipid mediators produced, whereas similarities between lipid profiles in blister fluid and epidermis indicated a primarily epidermal origin of suction blister fluid. Supplementation with omega-3 fatty acids ex vivo showed that their action is mediated through perturbation of existing species and formation of other anti-inflammatory lipids. These findings demonstrate the diversity of lipid mediators involved in maintaining tissue homeostasis in resting skin and hint at their contribution to signaling, cross-support, and functions of different skin compartments. Profiling lipid mediators in biopsies and suction blister fluid can support studies investigating cutaneous inflammatory responses, dietary manipulation, and skin diseases lacking biomarkers and therapeutic targets.

Mustard vesicants alter expression of the endocannabinoid system in mouse skin

“…They are thought to be important in regulating cell growth and differentiation, as well as in controlling skin inflammation (Biro et al, 2009; Kupczyk et al, 2009; Maccarrone et al, 2003). Endocannabinoids have also been detected in human skin suction blister fluid, presumably generated in response to trauma where they likely function to suppress inflammation and promote wound healing (Kendall et al, 2015). As NM and SM are skin blistering agents, endocannabinoids are also likely to be generated in vesicant-induced blisters.…”

Nrf2 deficiency causes lipid oxidation, inflammation, and matrix-protease expression in DHA-supplemented and UVA-irradiated skin fibroblasts

“…Short wave UVB (290nm -320 nm) can induce expression of COX-1, COX-2, 12-LOX and 15-LOX in human cultured keratinocytes and in whole skin [6]. UVA-2 (from 320 nm to 340 nm or 350 nm) seems to be the main responsible wavelength band to induce COX-2 expression, whereas the longer wavelength UVA-1 did not [18].…”

“…However, in the basal, living and proliferating layers of the epidermis and in cells of the underlying dermal compartment, a different variety of lipid mediators with a wide range of distinct functions are being uncovered. In these living layers fatty acid derived lipid mediators exert important signaling functions in homeostasis [6], ultraviolet stress responses (rev. in [7], inflammation [8] and disease [9] of the skin.…”

High-density lipoprotein deficiency in genetically modified mice deeply affects skin morphology: A structural and ultrastructural study

“…Lipids play a crucial role in the primary function of the skin as a barrier against water loss and pathogenic microorganisms [1]. In dermis and epidermis, the lipid content is different considering the various cell types herein represented.…”