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Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells

Background and purpose: Skin tissue is the natural barrier that protects our body, the damage of which can be repaired by the epidermal stem cells (ESCs). However, external factors abolish the self-repair ability of ESCs by inducing oxidative stress and severe inflammation. Apremilast is a small mol...

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Autores principales: Jia, Yuxi, Chen, Xiangru, Sun, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386542/
https://www.ncbi.nlm.nih.gov/pubmed/34375302
http://dx.doi.org/10.18632/aging.203265
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author Jia, Yuxi
Chen, Xiangru
Sun, Jing
author_facet Jia, Yuxi
Chen, Xiangru
Sun, Jing
author_sort Jia, Yuxi
collection PubMed
description Background and purpose: Skin tissue is the natural barrier that protects our body, the damage of which can be repaired by the epidermal stem cells (ESCs). However, external factors abolish the self-repair ability of ESCs by inducing oxidative stress and severe inflammation. Apremilast is a small molecular inhibitor of phosphodiesterase 4 that was approved for the treatment of psoriasis. In the present study, the protective property of Apremilast against IL-1α-induced dysfunction on epidermal stem cells, as well as the preliminary mechanism, will be investigated. Methods: ESCs were isolated from neonatal mice. The expression levels of TNF-α, IL-8, IL-12, MMP-2, and MMP-9 were detected using real-time PCR and ELISA. MitoSOX Red assay was used to determine the level of mitochondrial reactive oxygen species (ROS). Western blot and real-time PCR were utilized to determine the expression levels of IL-1R1, Myd88, and TRAF6. Activation of NF-κB was assessed by measuring the p-NF-κB p65 and luciferase activity. Capacities of ESCs were evaluated by measuring the gene expressions of integrin β1 and Krt19 using real-time PCR. Results: Firstly, the expression levels of TNF-α, IL-8, IL-12, MMP-2, MMP-9 and IL-1R1, as well as the ROS level, were significantly elevated by IL-1α but greatly suppressed by treatment with Apremilast. Subsequently, we found that the activated Myd88/TRAF6/NF-κB signaling pathway induced by stimulation with IL-1α was significantly inhibited by the introduction of Apremilast. As a result, Apremilast protected ESCs against IL-1α-induced impairment in capacities of ESCs, this was verified by the elevated expression levels of integrin β1 and Krt19. Conclusions: Apremilast might ameliorate IL-1α-induced dysfunction in ESCs by mitigating oxidative stress and inflammation through inhibiting the activation of the Myd88/TRAF6/NF-κB signaling pathway.
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spelling pubmed-83865422021-08-27 Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells Jia, Yuxi Chen, Xiangru Sun, Jing Aging (Albany NY) Research Paper Background and purpose: Skin tissue is the natural barrier that protects our body, the damage of which can be repaired by the epidermal stem cells (ESCs). However, external factors abolish the self-repair ability of ESCs by inducing oxidative stress and severe inflammation. Apremilast is a small molecular inhibitor of phosphodiesterase 4 that was approved for the treatment of psoriasis. In the present study, the protective property of Apremilast against IL-1α-induced dysfunction on epidermal stem cells, as well as the preliminary mechanism, will be investigated. Methods: ESCs were isolated from neonatal mice. The expression levels of TNF-α, IL-8, IL-12, MMP-2, and MMP-9 were detected using real-time PCR and ELISA. MitoSOX Red assay was used to determine the level of mitochondrial reactive oxygen species (ROS). Western blot and real-time PCR were utilized to determine the expression levels of IL-1R1, Myd88, and TRAF6. Activation of NF-κB was assessed by measuring the p-NF-κB p65 and luciferase activity. Capacities of ESCs were evaluated by measuring the gene expressions of integrin β1 and Krt19 using real-time PCR. Results: Firstly, the expression levels of TNF-α, IL-8, IL-12, MMP-2, MMP-9 and IL-1R1, as well as the ROS level, were significantly elevated by IL-1α but greatly suppressed by treatment with Apremilast. Subsequently, we found that the activated Myd88/TRAF6/NF-κB signaling pathway induced by stimulation with IL-1α was significantly inhibited by the introduction of Apremilast. As a result, Apremilast protected ESCs against IL-1α-induced impairment in capacities of ESCs, this was verified by the elevated expression levels of integrin β1 and Krt19. Conclusions: Apremilast might ameliorate IL-1α-induced dysfunction in ESCs by mitigating oxidative stress and inflammation through inhibiting the activation of the Myd88/TRAF6/NF-κB signaling pathway. Impact Journals 2021-08-10 /pmc/articles/PMC8386542/ /pubmed/34375302 http://dx.doi.org/10.18632/aging.203265 Text en Copyright: © 2021 Jia et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jia, Yuxi
Chen, Xiangru
Sun, Jing
Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells
title Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells
title_full Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells
title_fullStr Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells
title_full_unstemmed Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells
title_short Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells
title_sort apremilast ameliorates il-1α-induced dysfunction in epidermal stem cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386542/
https://www.ncbi.nlm.nih.gov/pubmed/34375302
http://dx.doi.org/10.18632/aging.203265
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