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Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea

Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers is increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cau...

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Autores principales: Muto, Yumiko, Wang, Zhenping, Vanderberghe, Matthieu, Two, Aimee, Gallo, Richard L., Di Nardo, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199909/
https://www.ncbi.nlm.nih.gov/pubmed/24844861
http://dx.doi.org/10.1038/jid.2014.222
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author Muto, Yumiko
Wang, Zhenping
Vanderberghe, Matthieu
Two, Aimee
Gallo, Richard L.
Di Nardo, Anna
author_facet Muto, Yumiko
Wang, Zhenping
Vanderberghe, Matthieu
Two, Aimee
Gallo, Richard L.
Di Nardo, Anna
author_sort Muto, Yumiko
collection PubMed
description Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers is increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cause vasodilation and angiogenesis. MCs are also one of the primary sources of cathelicidin LL-37 (Cath LL-37), an antimicrobial peptide that has been shown to be an enabler of rosacea pathogenesis. Here, we demonstrate that MCs are key mediators of cathelicidin initiated skin inflammation. Following Cath LL-37 injection into the dermis, MC deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (KitW-sh) mice did not develop rosacea-like features. Conversely, chymase (p<0.001), tryptase and Mmp9 (p<0.01) mRNA levels were significantly higher in C57BL/6 Wild Type (WT) mice. Treating WT mice with a MC stabilizer significantly decreased the expressions of Mmp9 and Cxcl2 (p<0.01). Our data was confirmed on Erythematotelangiectatic rosacea subjects that showed a decrease in MMP activity (p<0.05), after eight weeks of topical cromolyn treatment. We conclude that MCs play a central role in the development of inflammation subsequent to Cath LL-37 activation and that down regulation of activated MCs may be a therapy for rosacea treatment.
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spelling pubmed-41999092015-05-01 Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea Muto, Yumiko Wang, Zhenping Vanderberghe, Matthieu Two, Aimee Gallo, Richard L. Di Nardo, Anna J Invest Dermatol Article Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers is increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cause vasodilation and angiogenesis. MCs are also one of the primary sources of cathelicidin LL-37 (Cath LL-37), an antimicrobial peptide that has been shown to be an enabler of rosacea pathogenesis. Here, we demonstrate that MCs are key mediators of cathelicidin initiated skin inflammation. Following Cath LL-37 injection into the dermis, MC deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (KitW-sh) mice did not develop rosacea-like features. Conversely, chymase (p<0.001), tryptase and Mmp9 (p<0.01) mRNA levels were significantly higher in C57BL/6 Wild Type (WT) mice. Treating WT mice with a MC stabilizer significantly decreased the expressions of Mmp9 and Cxcl2 (p<0.01). Our data was confirmed on Erythematotelangiectatic rosacea subjects that showed a decrease in MMP activity (p<0.05), after eight weeks of topical cromolyn treatment. We conclude that MCs play a central role in the development of inflammation subsequent to Cath LL-37 activation and that down regulation of activated MCs may be a therapy for rosacea treatment. 2014-05-20 2014-11 /pmc/articles/PMC4199909/ /pubmed/24844861 http://dx.doi.org/10.1038/jid.2014.222 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Muto, Yumiko
Wang, Zhenping
Vanderberghe, Matthieu
Two, Aimee
Gallo, Richard L.
Di Nardo, Anna
Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea
title Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea
title_full Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea
title_fullStr Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea
title_full_unstemmed Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea
title_short Mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea
title_sort mast cells are key mediators of cathelicidin initiated skin inflammation in rosacea
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199909/
https://www.ncbi.nlm.nih.gov/pubmed/24844861
http://dx.doi.org/10.1038/jid.2014.222
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