Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes

Abstract Bleomycin hydrolase (BLMH) is a well-conserved cysteine protease widely expressed in several mammalian tissues. In skin, which contains high levels of BLMH, this protease is involved in the degradation of citrullinated filaggrin monomers into free amino acids important for skin hydration. I...

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Autores principales:	Rebecca Riise, Lina Odqvist, Johan Mattsson, Susan Monkley, Suado M. Abdillahi, Christian Tyrchan, Daniel Muthas, Linda Fahlén Yrlid
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ceb017fc1e6044e49f5970a9536755f0
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spelling	oai:doaj.org-article:ceb017fc1e6044e49f5970a9536755f02021-12-02T15:12:22ZBleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes10.1038/s41598-019-56667-62045-2322https://doaj.org/article/ceb017fc1e6044e49f5970a9536755f02019-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-56667-6https://doaj.org/toc/2045-2322Abstract Bleomycin hydrolase (BLMH) is a well-conserved cysteine protease widely expressed in several mammalian tissues. In skin, which contains high levels of BLMH, this protease is involved in the degradation of citrullinated filaggrin monomers into free amino acids important for skin hydration. Interestingly, the expression and activity of BLMH is reduced in patients with atopic dermatitis (AD) and psoriasis, and BLMH knockout mice acquire tail dermatitis. Apart from its already known function, we have discovered a novel role of BLMH in the regulation of inflammatory chemokines and wound healing. We show that lowered BLMH levels in keratinocytes result in increased release of the pro-inflammatory chemokines CXCL8 and GROα, which are upregulated in skin from AD patients compared to healthy individuals. Conditioned media from keratinocytes expressing low levels of BLMH increased chemotaxis by neutrophils and caused a delayed wound healing in the presence of low-level TNFα. This defective wound healing was improved by blocking the shared receptor of CXCL8 and GROα, namely CXCR2, using a specific receptor antagonist. Collectively, our results present a novel function of BLMH in regulating the secretion of chemokines involved in inflammation and wound healing in human keratinocytes.Rebecca RiiseLina OdqvistJohan MattssonSusan MonkleySuado M. AbdillahiChristian TyrchanDaniel MuthasLinda Fahlén YrlidNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rebecca Riise Lina Odqvist Johan Mattsson Susan Monkley Suado M. Abdillahi Christian Tyrchan Daniel Muthas Linda Fahlén Yrlid Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
description	Abstract Bleomycin hydrolase (BLMH) is a well-conserved cysteine protease widely expressed in several mammalian tissues. In skin, which contains high levels of BLMH, this protease is involved in the degradation of citrullinated filaggrin monomers into free amino acids important for skin hydration. Interestingly, the expression and activity of BLMH is reduced in patients with atopic dermatitis (AD) and psoriasis, and BLMH knockout mice acquire tail dermatitis. Apart from its already known function, we have discovered a novel role of BLMH in the regulation of inflammatory chemokines and wound healing. We show that lowered BLMH levels in keratinocytes result in increased release of the pro-inflammatory chemokines CXCL8 and GROα, which are upregulated in skin from AD patients compared to healthy individuals. Conditioned media from keratinocytes expressing low levels of BLMH increased chemotaxis by neutrophils and caused a delayed wound healing in the presence of low-level TNFα. This defective wound healing was improved by blocking the shared receptor of CXCL8 and GROα, namely CXCR2, using a specific receptor antagonist. Collectively, our results present a novel function of BLMH in regulating the secretion of chemokines involved in inflammation and wound healing in human keratinocytes.
format	article
author	Rebecca Riise Lina Odqvist Johan Mattsson Susan Monkley Suado M. Abdillahi Christian Tyrchan Daniel Muthas Linda Fahlén Yrlid
author_facet	Rebecca Riise Lina Odqvist Johan Mattsson Susan Monkley Suado M. Abdillahi Christian Tyrchan Daniel Muthas Linda Fahlén Yrlid
author_sort	Rebecca Riise
title	Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
title_short	Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
title_full	Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
title_fullStr	Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
title_full_unstemmed	Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
title_sort	bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ceb017fc1e6044e49f5970a9536755f0
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Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes

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