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The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2
Keratinocytes (KC) play a crucial role in epidermal barrier function, notably through their metabolic activity and the detection of danger signals. Chemical sensitizers are known to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), leading to cellular detoxificati...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945052/ https://www.ncbi.nlm.nih.gov/pubmed/35326225 http://dx.doi.org/10.3390/antiox11030575 |
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author | Vallion, Romain Hardonnière, Kévin Bouredji, Abderrahmane Damiens, Marie-Hélène Deloménie, Claudine Pallardy, Marc Ferret, Pierre-Jacques Kerdine-Römer, Saadia |
author_facet | Vallion, Romain Hardonnière, Kévin Bouredji, Abderrahmane Damiens, Marie-Hélène Deloménie, Claudine Pallardy, Marc Ferret, Pierre-Jacques Kerdine-Römer, Saadia |
author_sort | Vallion, Romain |
collection | PubMed |
description | Keratinocytes (KC) play a crucial role in epidermal barrier function, notably through their metabolic activity and the detection of danger signals. Chemical sensitizers are known to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), leading to cellular detoxification and suppressed proinflammatory cytokines such as IL-1β, a key cytokine in skin allergy. We investigated the role of Nrf2 in the control of the proinflammatory response in human KC following treatment with Cinnamaldehyde (CinA), a well-known skin sensitizer. We used the well-described human KC cell line KERTr exposed to CinA. Our results showed that 250 μM of CinA did not induce any Nrf2 accumulation but increased the expression of proinflammatory cytokines. In contrast, 100 μM of CinA induced a rapid accumulation of Nrf2, inhibited IL-1β transcription, and downregulated the zymosan-induced proinflammatory response. Moreover, Nrf2 knockdown KERTr cells (KERTr ko) showed an increase in proinflammatory cytokines. Since the inhibition of Nrf2 has been shown to alter cellular metabolism, we performed metabolomic and seahorse analyses. The results showed a decrease in mitochondrial metabolism following KERTr ko exposure to CinA 100 µM. In conclusion, the fate of Nrf2 controls proinflammatory cytokine production in KCs that could be linked to its capacity to preserve mitochondrial metabolism upon chemical sensitizer exposure. |
format | Online Article Text |
id | pubmed-8945052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89450522022-03-25 The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2 Vallion, Romain Hardonnière, Kévin Bouredji, Abderrahmane Damiens, Marie-Hélène Deloménie, Claudine Pallardy, Marc Ferret, Pierre-Jacques Kerdine-Römer, Saadia Antioxidants (Basel) Article Keratinocytes (KC) play a crucial role in epidermal barrier function, notably through their metabolic activity and the detection of danger signals. Chemical sensitizers are known to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), leading to cellular detoxification and suppressed proinflammatory cytokines such as IL-1β, a key cytokine in skin allergy. We investigated the role of Nrf2 in the control of the proinflammatory response in human KC following treatment with Cinnamaldehyde (CinA), a well-known skin sensitizer. We used the well-described human KC cell line KERTr exposed to CinA. Our results showed that 250 μM of CinA did not induce any Nrf2 accumulation but increased the expression of proinflammatory cytokines. In contrast, 100 μM of CinA induced a rapid accumulation of Nrf2, inhibited IL-1β transcription, and downregulated the zymosan-induced proinflammatory response. Moreover, Nrf2 knockdown KERTr cells (KERTr ko) showed an increase in proinflammatory cytokines. Since the inhibition of Nrf2 has been shown to alter cellular metabolism, we performed metabolomic and seahorse analyses. The results showed a decrease in mitochondrial metabolism following KERTr ko exposure to CinA 100 µM. In conclusion, the fate of Nrf2 controls proinflammatory cytokine production in KCs that could be linked to its capacity to preserve mitochondrial metabolism upon chemical sensitizer exposure. MDPI 2022-03-17 /pmc/articles/PMC8945052/ /pubmed/35326225 http://dx.doi.org/10.3390/antiox11030575 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Vallion, Romain Hardonnière, Kévin Bouredji, Abderrahmane Damiens, Marie-Hélène Deloménie, Claudine Pallardy, Marc Ferret, Pierre-Jacques Kerdine-Römer, Saadia The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2 |
title | The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2 |
title_full | The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2 |
title_fullStr | The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2 |
title_full_unstemmed | The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2 |
title_short | The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2 |
title_sort | inflammatory response in human keratinocytes exposed to cinnamaldehyde is regulated by nrf2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945052/ https://www.ncbi.nlm.nih.gov/pubmed/35326225 http://dx.doi.org/10.3390/antiox11030575 |
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