Cargando…

Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1

Background: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 express...

Descripción completa

Detalles Bibliográficos
Autores principales: Tsuji, Gaku, Hashimoto-Hachiya, Akiko, Yen, Vu Hai, Miake, Sho, Takemura, Masaki, Mitamura, Yasutaka, Ito, Takamichi, Murata, Maho, Furue, Masutaka, Nakahara, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141508/
https://www.ncbi.nlm.nih.gov/pubmed/32214018
http://dx.doi.org/10.3390/jcm9030891
_version_ 1783519208146993152
author Tsuji, Gaku
Hashimoto-Hachiya, Akiko
Yen, Vu Hai
Miake, Sho
Takemura, Masaki
Mitamura, Yasutaka
Ito, Takamichi
Murata, Maho
Furue, Masutaka
Nakahara, Takeshi
author_facet Tsuji, Gaku
Hashimoto-Hachiya, Akiko
Yen, Vu Hai
Miake, Sho
Takemura, Masaki
Mitamura, Yasutaka
Ito, Takamichi
Murata, Maho
Furue, Masutaka
Nakahara, Takeshi
author_sort Tsuji, Gaku
collection PubMed
description Background: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood. Methods: We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4. Results: IL-4 induced the upregulation of IL-33 expression in NHEKs. Based on the findings 1) that ovo-like 1 (OVOL1), a susceptible gene of AD, upregulates filaggrin (FLG) and loricrin (LOR) expression in NHEKs and 2) that reduced expression of FLG and LOR leads to production of IL-1 superfamily cytokines, we examined the involvement of OVOL1 in IL-33 expression in NHEKs. Knockdown of OVOL1 induced upregulation of IL-33 expression. Moreover, because Glyteer, an activator of aryl hydrocarbon receptor (AHR), reportedly upregulates OVOL1 expression, we examined whether treatment with Glyteer inhibited IL-33 expression in NHEKs. Treatment with Glyteer inhibited IL-4-induced upregulation of IL-33 expression, which was canceled by knockdown of either AHR or OVOL1. Conclusions: Activation of the AHR-OVOL1 axis inhibits IL-4-induced IL-33 expression, which could be beneficial for the treatment of AD.
format Online
Article
Text
id pubmed-7141508
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-71415082020-04-15 Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1 Tsuji, Gaku Hashimoto-Hachiya, Akiko Yen, Vu Hai Miake, Sho Takemura, Masaki Mitamura, Yasutaka Ito, Takamichi Murata, Maho Furue, Masutaka Nakahara, Takeshi J Clin Med Article Background: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood. Methods: We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4. Results: IL-4 induced the upregulation of IL-33 expression in NHEKs. Based on the findings 1) that ovo-like 1 (OVOL1), a susceptible gene of AD, upregulates filaggrin (FLG) and loricrin (LOR) expression in NHEKs and 2) that reduced expression of FLG and LOR leads to production of IL-1 superfamily cytokines, we examined the involvement of OVOL1 in IL-33 expression in NHEKs. Knockdown of OVOL1 induced upregulation of IL-33 expression. Moreover, because Glyteer, an activator of aryl hydrocarbon receptor (AHR), reportedly upregulates OVOL1 expression, we examined whether treatment with Glyteer inhibited IL-33 expression in NHEKs. Treatment with Glyteer inhibited IL-4-induced upregulation of IL-33 expression, which was canceled by knockdown of either AHR or OVOL1. Conclusions: Activation of the AHR-OVOL1 axis inhibits IL-4-induced IL-33 expression, which could be beneficial for the treatment of AD. MDPI 2020-03-24 /pmc/articles/PMC7141508/ /pubmed/32214018 http://dx.doi.org/10.3390/jcm9030891 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
Tsuji, Gaku
Hashimoto-Hachiya, Akiko
Yen, Vu Hai
Miake, Sho
Takemura, Masaki
Mitamura, Yasutaka
Ito, Takamichi
Murata, Maho
Furue, Masutaka
Nakahara, Takeshi
Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
title Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
title_full Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
title_fullStr Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
title_full_unstemmed Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
title_short Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
title_sort aryl hydrocarbon receptor activation downregulates il-33 expression in keratinocytes via ovo-like 1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141508/
https://www.ncbi.nlm.nih.gov/pubmed/32214018
http://dx.doi.org/10.3390/jcm9030891
work_keys_str_mv AT tsujigaku arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT hashimotohachiyaakiko arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT yenvuhai arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT miakesho arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT takemuramasaki arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT mitamurayasutaka arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT itotakamichi arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT muratamaho arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT furuemasutaka arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1
AT nakaharatakeshi arylhydrocarbonreceptoractivationdownregulatesil33expressioninkeratinocytesviaovolike1