Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway

Matrix stiffness, a critical physical property of the cellular environment, is implicated in epidermal homeostasis. In particular, matrix stiffening during the pathological progression of skin diseases appears to contribute to cellular responses of keratinocytes. However, it has not yet elucidated t...

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Autores principales:	Hyewon Chung, Seunghee Oh, Hyun-Woo Shin, Yunam Lee, Hyungsuk Lee, Seung Hyeok Seok
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	skin keratinocyte inflammatory response IL-6 matrix stiffening Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/d9e1f0c2dfe2413aafe9493609e11797
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spelling	oai:doaj.org-article:d9e1f0c2dfe2413aafe9493609e117972021-11-11T06:13:26ZMatrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway1664-322410.3389/fimmu.2021.759992https://doaj.org/article/d9e1f0c2dfe2413aafe9493609e117972021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.759992/fullhttps://doaj.org/toc/1664-3224Matrix stiffness, a critical physical property of the cellular environment, is implicated in epidermal homeostasis. In particular, matrix stiffening during the pathological progression of skin diseases appears to contribute to cellular responses of keratinocytes. However, it has not yet elucidated the molecular mechanism underlying matrix-stiffness-mediated signaling in coordination with chemical stimuli during inflammation and its effect on proinflammatory cytokine production. In this study, we demonstrated that keratinocytes adapt to matrix stiffening by increasing cell–matrix adhesion via actin cytoskeleton remodeling. Specifically, mechanosensing and signal transduction are coupled with chemical stimuli to regulate cytokine production, and interleukin-6 (IL-6) production is elevated in keratinocytes on stiffer substrates in response to 2,4-dinitrochlorobenzene. We demonstrated that β1 integrin and focal adhesion kinase (FAK) expression were enhanced with increasing stiffness and activation of ERK and the PI3K/Akt pathway was involved in stiffening-mediated IL-6 production. Collectively, our results reveal the critical role of matrix stiffening in modulating the proinflammatory response of keratinocytes, with important clinical implications for skin diseases accompanied by pathological matrix stiffening.Hyewon ChungSeunghee OhSeunghee OhHyun-Woo ShinHyun-Woo ShinYunam LeeHyungsuk LeeSeung Hyeok SeokSeung Hyeok SeokFrontiers Media S.A.articleskinkeratinocyteinflammatory responseIL-6matrix stiffeningImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	skin keratinocyte inflammatory response IL-6 matrix stiffening Immunologic diseases. Allergy RC581-607
spellingShingle	skin keratinocyte inflammatory response IL-6 matrix stiffening Immunologic diseases. Allergy RC581-607 Hyewon Chung Seunghee Oh Seunghee Oh Hyun-Woo Shin Hyun-Woo Shin Yunam Lee Hyungsuk Lee Seung Hyeok Seok Seung Hyeok Seok Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway
description	Matrix stiffness, a critical physical property of the cellular environment, is implicated in epidermal homeostasis. In particular, matrix stiffening during the pathological progression of skin diseases appears to contribute to cellular responses of keratinocytes. However, it has not yet elucidated the molecular mechanism underlying matrix-stiffness-mediated signaling in coordination with chemical stimuli during inflammation and its effect on proinflammatory cytokine production. In this study, we demonstrated that keratinocytes adapt to matrix stiffening by increasing cell–matrix adhesion via actin cytoskeleton remodeling. Specifically, mechanosensing and signal transduction are coupled with chemical stimuli to regulate cytokine production, and interleukin-6 (IL-6) production is elevated in keratinocytes on stiffer substrates in response to 2,4-dinitrochlorobenzene. We demonstrated that β1 integrin and focal adhesion kinase (FAK) expression were enhanced with increasing stiffness and activation of ERK and the PI3K/Akt pathway was involved in stiffening-mediated IL-6 production. Collectively, our results reveal the critical role of matrix stiffening in modulating the proinflammatory response of keratinocytes, with important clinical implications for skin diseases accompanied by pathological matrix stiffening.
format	article
author	Hyewon Chung Seunghee Oh Seunghee Oh Hyun-Woo Shin Hyun-Woo Shin Yunam Lee Hyungsuk Lee Seung Hyeok Seok Seung Hyeok Seok
author_facet	Hyewon Chung Seunghee Oh Seunghee Oh Hyun-Woo Shin Hyun-Woo Shin Yunam Lee Hyungsuk Lee Seung Hyeok Seok Seung Hyeok Seok
author_sort	Hyewon Chung
title	Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway
title_short	Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway
title_full	Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway
title_fullStr	Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway
title_full_unstemmed	Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway
title_sort	matrix stiffening enhances dncb-induced il-6 secretion in keratinocytes through activation of erk and pi3k/akt pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d9e1f0c2dfe2413aafe9493609e11797
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Matrix Stiffening Enhances DNCB-Induced IL-6 Secretion in Keratinocytes Through Activation of ERK and PI3K/Akt Pathway

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