N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model

• Published in: Scientific reports Vol. 13; no. 1; p. 12113
• Main Authors: Simard, Mélissa, Tremblay, Andréa, Morin, Sophie, Rioux, Geneviève, Flamand, Nicolas, Pouliot, Roxane
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-07-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 639/166/985; 692/420/256; 692/699/4033; Cannabinoid CB1 receptors; Cell Proliferation; Endocannabinoid system; Ethanolamine; Ethanolamine - metabolism; Ethanolamines - metabolism; Ethanolamines - pharmacology; Glycerol; Humanities and Social Sciences; Humans; Keratinocytes; Keratinocytes - metabolism; Linolenic acid; Lipid metabolism; Monoacylglycerol Lipases - metabolism; multidisciplinary; Phenotypes; Polyunsaturated fatty acids; Psoriasis; Psoriasis - drug therapy; Psoriasis - metabolism; Science; Science (multidisciplinary); Skin - metabolism; Skin diseases; Tissue engineering
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-39185-4

Psoriasis is an inflammatory skin disease that is characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation and dysregulated lipid metabolism. Some lipid mediators of the
N
-acylethanolamines (NAEs) and monoacylglycerols (MAGs) can bind to cannabinoid (CB) receptors and are referred to as part of the endocannabinoidome. Their implication in psoriasis remains unknown. The aim of the present study was to characterize the endocannabinoid system and evaluate the effects of n-3-derived NAEs, namely
N
-eicosapentaenoyl-ethanolamine (EPEA), in psoriatic keratinocytes using a psoriatic skin model produced by tissue engineering, following the self-assembly method. Psoriatic skin substitutes had lower
FAAH2
expression and higher
MAGL
,
ABHD6
and
ABHD12
expression compared with healthy skin substitutes. Treatments with alpha-linolenic acid (ALA) increased the levels of EPEA and 1/2-docosapentaenoyl-glycerol, showing that levels of n-3 polyunsaturated fatty acids modulate related NAE and MAG levels. Treatments of the psoriatic substitutes with 10 μM of EPEA for 7 days resulted in decreased epidermal thickness and number of Ki67 positive keratinocytes, both indicating decreased proliferation of psoriatic keratinocytes. EPEA effects on keratinocyte proliferation were inhibited by the CB
1
receptor antagonist rimonabant. Exogenous EPEA also diminished some inflammatory features of psoriasis. In summary, n-3-derived NAEs can reduce the psoriatic phenotype of a reconstructed psoriatic skin model.