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Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation

Aryl hydrocarbon receptor (AhR) and autophagy reportedly regulate immune responses in the skin. This study explored the effects of AhR activation on autophagy in human keratinocytes, and the relevance of AhR and autophagy in psoriasis pathogenesis. AhR activation by 2,3,7,8-Tetrachlorodibenzo-p-diox...

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Autores principales: Kim, Hye Ran, Kang, Seok Young, Kim, Hye One, Park, Chun Wook, Chung, Bo Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139675/
https://www.ncbi.nlm.nih.gov/pubmed/32235789
http://dx.doi.org/10.3390/ijms21062195
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author Kim, Hye Ran
Kang, Seok Young
Kim, Hye One
Park, Chun Wook
Chung, Bo Young
author_facet Kim, Hye Ran
Kang, Seok Young
Kim, Hye One
Park, Chun Wook
Chung, Bo Young
author_sort Kim, Hye Ran
collection PubMed
description Aryl hydrocarbon receptor (AhR) and autophagy reportedly regulate immune responses in the skin. This study explored the effects of AhR activation on autophagy in human keratinocytes, and the relevance of AhR and autophagy in psoriasis pathogenesis. AhR activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) repressed autophagy, while autophagy inhibition induced AhR activation in HaCaT cells and normal human epidermal keratinocytes (NHEKs). A particularly strong interaction between AhR and autophagy was observed in proinflammatory cytokines-stimulated keratinocytes, an in vitro model of psoriasis. In skin biopsies from psoriasis patients, a similar impact of AhR on autophagy and inflammation was observed. AhR inhibition blocked TCDD- and chloroquine-induced p65NF-κB and p38MAPK phosphorylation in proinflammatory cytokines-stimulated HaCaT cells. Moreover, higher expression of AhR and CYP1A1, and lower expression of LC3, were detected in psoriatic skin tissues, compared to the controls. These data demonstrated that AhR modulated autophagy leads to skin inflammation in human keratinocytes via the p65NF-κB/p38MAPK signaling pathways, suggesting that AhR signaling and autophagy might be involved in the pathogenesis of chronic inflammatory disorders such as psoriasis.
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spelling pubmed-71396752020-04-10 Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation Kim, Hye Ran Kang, Seok Young Kim, Hye One Park, Chun Wook Chung, Bo Young Int J Mol Sci Article Aryl hydrocarbon receptor (AhR) and autophagy reportedly regulate immune responses in the skin. This study explored the effects of AhR activation on autophagy in human keratinocytes, and the relevance of AhR and autophagy in psoriasis pathogenesis. AhR activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) repressed autophagy, while autophagy inhibition induced AhR activation in HaCaT cells and normal human epidermal keratinocytes (NHEKs). A particularly strong interaction between AhR and autophagy was observed in proinflammatory cytokines-stimulated keratinocytes, an in vitro model of psoriasis. In skin biopsies from psoriasis patients, a similar impact of AhR on autophagy and inflammation was observed. AhR inhibition blocked TCDD- and chloroquine-induced p65NF-κB and p38MAPK phosphorylation in proinflammatory cytokines-stimulated HaCaT cells. Moreover, higher expression of AhR and CYP1A1, and lower expression of LC3, were detected in psoriatic skin tissues, compared to the controls. These data demonstrated that AhR modulated autophagy leads to skin inflammation in human keratinocytes via the p65NF-κB/p38MAPK signaling pathways, suggesting that AhR signaling and autophagy might be involved in the pathogenesis of chronic inflammatory disorders such as psoriasis. MDPI 2020-03-22 /pmc/articles/PMC7139675/ /pubmed/32235789 http://dx.doi.org/10.3390/ijms21062195 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Hye Ran
Kang, Seok Young
Kim, Hye One
Park, Chun Wook
Chung, Bo Young
Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation
title Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation
title_full Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation
title_fullStr Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation
title_full_unstemmed Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation
title_short Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation
title_sort role of aryl hydrocarbon receptor activation and autophagy in psoriasis-related inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139675/
https://www.ncbi.nlm.nih.gov/pubmed/32235789
http://dx.doi.org/10.3390/ijms21062195
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