Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.

<h4>Background</h4>Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger a...

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Autores principales:	Philipp R Esser, Ute Wölfle, Christoph Dürr, Friederike D von Loewenich, Christoph M Schempp, Marina A Freudenberg, Thilo Jakob, Stefan F Martin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/53c6188ca9cc4c91b69c3d445dad070e
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spelling	oai:doaj.org-article:53c6188ca9cc4c91b69c3d445dad070e2021-11-18T07:11:09ZContact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.1932-620310.1371/journal.pone.0041340https://doaj.org/article/53c6188ca9cc4c91b69c3d445dad070e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848468/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses.<h4>Methodology/principal findings</h4>We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS) and a concomitant breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS.<h4>Conclusions/significance</h4>These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD.Philipp R EsserUte WölfleChristoph DürrFriederike D von LoewenichChristoph M SchemppMarina A FreudenbergThilo JakobStefan F MartinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41340 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philipp R Esser Ute Wölfle Christoph Dürr Friederike D von Loewenich Christoph M Schempp Marina A Freudenberg Thilo Jakob Stefan F Martin Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.
description	<h4>Background</h4>Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses.<h4>Methodology/principal findings</h4>We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS) and a concomitant breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS.<h4>Conclusions/significance</h4>These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD.
format	article
author	Philipp R Esser Ute Wölfle Christoph Dürr Friederike D von Loewenich Christoph M Schempp Marina A Freudenberg Thilo Jakob Stefan F Martin
author_facet	Philipp R Esser Ute Wölfle Christoph Dürr Friederike D von Loewenich Christoph M Schempp Marina A Freudenberg Thilo Jakob Stefan F Martin
author_sort	Philipp R Esser
title	Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.
title_short	Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.
title_full	Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.
title_fullStr	Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.
title_full_unstemmed	Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.
title_sort	contact sensitizers induce skin inflammation via ros production and hyaluronic acid degradation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/53c6188ca9cc4c91b69c3d445dad070e
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Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.

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