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Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes
The vicious itch–scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651282/ https://www.ncbi.nlm.nih.gov/pubmed/31284553 http://dx.doi.org/10.3390/ijms20133324 |
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author | Ulzii, Dugarmaa Kido-Nakahara, Makiko Nakahara, Takeshi Tsuji, Gaku Furue, Kazuhisa Hashimoto-Hachiya, Akiko Furue, Masutaka |
author_facet | Ulzii, Dugarmaa Kido-Nakahara, Makiko Nakahara, Takeshi Tsuji, Gaku Furue, Kazuhisa Hashimoto-Hachiya, Akiko Furue, Masutaka |
author_sort | Ulzii, Dugarmaa |
collection | PubMed |
description | The vicious itch–scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works as a nonfunctional decoy receptor. To examine whether scratch injury affects the expression of IL-4Rα, IL-13Rα1, and IL-13Rα2, we scratched confluent keratinocyte sheets and examined the expression of three IL-13 receptors using quantitative real-time PCR (qRT-PCR) and immunofluorescence techniques. Scratch injuries significantly upregulated the expression of IL13RA2 in a scratch line number-dependent manner. Scratch-induced IL13RA2 upregulation was synergistically enhanced in the simultaneous presence of IL-13. In contrast, scratch injuries did not alter the expression of IL4R and IL13RA1, even in the presence of IL-13. Scratch-induced IL13RA2 expression was dependent on ERK1/2 and p38 MAPK signals. The expression of IL-13Rα2 protein was indeed augmented in the scratch edge area and was also overexpressed in lichenified lesional AD skin. IL-13 inhibited the expression of involucrin, an important epidermal terminal differentiation molecule. IL-13-mediated downregulation of involucrin was attenuated in IL-13Rα2-overexpressed keratinocytes, confirming the decoy function of IL-13Rα2. Our findings indicate that scratching upregulates the expression of the IL-13 decoy receptor IL-13Rα2 and counteracts IL-13 signaling. |
format | Online Article Text |
id | pubmed-6651282 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66512822019-08-07 Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes Ulzii, Dugarmaa Kido-Nakahara, Makiko Nakahara, Takeshi Tsuji, Gaku Furue, Kazuhisa Hashimoto-Hachiya, Akiko Furue, Masutaka Int J Mol Sci Article The vicious itch–scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works as a nonfunctional decoy receptor. To examine whether scratch injury affects the expression of IL-4Rα, IL-13Rα1, and IL-13Rα2, we scratched confluent keratinocyte sheets and examined the expression of three IL-13 receptors using quantitative real-time PCR (qRT-PCR) and immunofluorescence techniques. Scratch injuries significantly upregulated the expression of IL13RA2 in a scratch line number-dependent manner. Scratch-induced IL13RA2 upregulation was synergistically enhanced in the simultaneous presence of IL-13. In contrast, scratch injuries did not alter the expression of IL4R and IL13RA1, even in the presence of IL-13. Scratch-induced IL13RA2 expression was dependent on ERK1/2 and p38 MAPK signals. The expression of IL-13Rα2 protein was indeed augmented in the scratch edge area and was also overexpressed in lichenified lesional AD skin. IL-13 inhibited the expression of involucrin, an important epidermal terminal differentiation molecule. IL-13-mediated downregulation of involucrin was attenuated in IL-13Rα2-overexpressed keratinocytes, confirming the decoy function of IL-13Rα2. Our findings indicate that scratching upregulates the expression of the IL-13 decoy receptor IL-13Rα2 and counteracts IL-13 signaling. MDPI 2019-07-06 /pmc/articles/PMC6651282/ /pubmed/31284553 http://dx.doi.org/10.3390/ijms20133324 Text en © 2019 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 Ulzii, Dugarmaa Kido-Nakahara, Makiko Nakahara, Takeshi Tsuji, Gaku Furue, Kazuhisa Hashimoto-Hachiya, Akiko Furue, Masutaka Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes |
title | Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes |
title_full | Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes |
title_fullStr | Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes |
title_full_unstemmed | Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes |
title_short | Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes |
title_sort | scratching counteracts il-13 signaling by upregulating the decoy receptor il-13rα2 in keratinocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651282/ https://www.ncbi.nlm.nih.gov/pubmed/31284553 http://dx.doi.org/10.3390/ijms20133324 |
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