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N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371979/ https://www.ncbi.nlm.nih.gov/pubmed/37495686 http://dx.doi.org/10.1038/s41598-023-39185-4 |
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author | Simard, Mélissa Tremblay, Andréa Morin, Sophie Rioux, Geneviève Flamand, Nicolas Pouliot, Roxane |
author_facet | Simard, Mélissa Tremblay, Andréa Morin, Sophie Rioux, Geneviève Flamand, Nicolas Pouliot, Roxane |
author_sort | Simard, Mélissa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10371979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103719792023-07-28 N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model Simard, Mélissa Tremblay, Andréa Morin, Sophie Rioux, Geneviève Flamand, Nicolas Pouliot, Roxane Sci Rep Article 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. Nature Publishing Group UK 2023-07-26 /pmc/articles/PMC10371979/ /pubmed/37495686 http://dx.doi.org/10.1038/s41598-023-39185-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Simard, Mélissa Tremblay, Andréa Morin, Sophie Rioux, Geneviève Flamand, Nicolas Pouliot, Roxane N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
title | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
title_full | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
title_fullStr | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
title_full_unstemmed | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
title_short | N-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
title_sort | n-eicosapentaenoyl-ethanolamine decreases the proliferation of psoriatic keratinocytes in a reconstructed psoriatic skin model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371979/ https://www.ncbi.nlm.nih.gov/pubmed/37495686 http://dx.doi.org/10.1038/s41598-023-39185-4 |
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