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Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis
BACKGROUND: Atopic dermatitis (AD) is characterized by chronic, relapsing skin inflammation (eczema) with itchy sensation. Keratinocytes, which are located at the outermost part of our body, are supposed to play important roles at the early phase of type 2 inflammation including AD pathogenesis. OBJ...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Dermatological Association; The Korean Society for Investigative Dermatology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875219/ https://www.ncbi.nlm.nih.gov/pubmed/33911809 http://dx.doi.org/10.5021/ad.2021.33.1.26 |
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author | Choi, Da-In Park, Jun-Hyeong Choi, Jee-Young Piao, MeiShan Suh, Min-Song Lee, Jee-Bum Yun, Sook-Jung Lee, Seung-Chul |
author_facet | Choi, Da-In Park, Jun-Hyeong Choi, Jee-Young Piao, MeiShan Suh, Min-Song Lee, Jee-Bum Yun, Sook-Jung Lee, Seung-Chul |
author_sort | Choi, Da-In |
collection | PubMed |
description | BACKGROUND: Atopic dermatitis (AD) is characterized by chronic, relapsing skin inflammation (eczema) with itchy sensation. Keratinocytes, which are located at the outermost part of our body, are supposed to play important roles at the early phase of type 2 inflammation including AD pathogenesis. OBJECTIVE: The purpose of this study was to evaluate whether keratinocytes-derived reactive oxygen species (ROS) could be produced by the allergens or non-allergens, and the keratinocytes-derived ROS could modulate a set of biomarkers for type 2 inflammation of the skin. METHODS: Normal human epidermal keratinocytes (NHEKs) were treated with an allergen of house dust mites (HDM) or a non-allergen of compound 48/80 (C48/80). Then, biomarkers for type 2 inflammation of the skin including those for neurogenic inflammation were checked by reverse transcriptase-polymerase chain reaction and western immunoblot experiments. RESULTS: HDM or C48/80 was found to upregulate expression levels of our tested biomarkers, including type 2 T helper-driving pathway (KLK5, PAR2, and NFκB), epithelial-cell-derived cytokines (thymic stromal lymphopoietin, interleukin [IL]-25, IL-33), and neurogenic inflammation (NGF, CGRP). The HDM- or C-48/80-induced expression levels of the biomarkers could be blocked by an antioxidant treatment with 5 mM N-acetyl-cysteine. In contrast, pro-oxidant treatment with 1 mM H(2)O(2) could upregulate expression levels of the tested biomarkers in NHEKs. CONCLUSION: Our results reveal that keratinocytes-derived ROS, irrespective to their origins from allergens or non-allergens, have a potential to induce type 2 inflammation of AD skin. |
format | Online Article Text |
id | pubmed-7875219 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Korean Dermatological Association; The Korean Society for Investigative Dermatology |
record_format | MEDLINE/PubMed |
spelling | pubmed-78752192021-04-27 Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis Choi, Da-In Park, Jun-Hyeong Choi, Jee-Young Piao, MeiShan Suh, Min-Song Lee, Jee-Bum Yun, Sook-Jung Lee, Seung-Chul Ann Dermatol Original Article BACKGROUND: Atopic dermatitis (AD) is characterized by chronic, relapsing skin inflammation (eczema) with itchy sensation. Keratinocytes, which are located at the outermost part of our body, are supposed to play important roles at the early phase of type 2 inflammation including AD pathogenesis. OBJECTIVE: The purpose of this study was to evaluate whether keratinocytes-derived reactive oxygen species (ROS) could be produced by the allergens or non-allergens, and the keratinocytes-derived ROS could modulate a set of biomarkers for type 2 inflammation of the skin. METHODS: Normal human epidermal keratinocytes (NHEKs) were treated with an allergen of house dust mites (HDM) or a non-allergen of compound 48/80 (C48/80). Then, biomarkers for type 2 inflammation of the skin including those for neurogenic inflammation were checked by reverse transcriptase-polymerase chain reaction and western immunoblot experiments. RESULTS: HDM or C48/80 was found to upregulate expression levels of our tested biomarkers, including type 2 T helper-driving pathway (KLK5, PAR2, and NFκB), epithelial-cell-derived cytokines (thymic stromal lymphopoietin, interleukin [IL]-25, IL-33), and neurogenic inflammation (NGF, CGRP). The HDM- or C-48/80-induced expression levels of the biomarkers could be blocked by an antioxidant treatment with 5 mM N-acetyl-cysteine. In contrast, pro-oxidant treatment with 1 mM H(2)O(2) could upregulate expression levels of the tested biomarkers in NHEKs. CONCLUSION: Our results reveal that keratinocytes-derived ROS, irrespective to their origins from allergens or non-allergens, have a potential to induce type 2 inflammation of AD skin. The Korean Dermatological Association; The Korean Society for Investigative Dermatology 2021-02 2020-12-30 /pmc/articles/PMC7875219/ /pubmed/33911809 http://dx.doi.org/10.5021/ad.2021.33.1.26 Text en Copyright © 2021 The Korean Dermatological Association and The Korean Society for Investigative Dermatology http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Choi, Da-In Park, Jun-Hyeong Choi, Jee-Young Piao, MeiShan Suh, Min-Song Lee, Jee-Bum Yun, Sook-Jung Lee, Seung-Chul Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis |
title | Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis |
title_full | Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis |
title_fullStr | Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis |
title_full_unstemmed | Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis |
title_short | Keratinocytes-Derived Reactive Oxygen Species Play an Active Role to Induce Type 2 Inflammation of the Skin: A Pathogenic Role of Reactive Oxygen Species at the Early Phase of Atopic Dermatitis |
title_sort | keratinocytes-derived reactive oxygen species play an active role to induce type 2 inflammation of the skin: a pathogenic role of reactive oxygen species at the early phase of atopic dermatitis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875219/ https://www.ncbi.nlm.nih.gov/pubmed/33911809 http://dx.doi.org/10.5021/ad.2021.33.1.26 |
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