Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells

Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells

Histone deacetylases (HDAC) are key enzymes in the epigenetic control of gene expression. Recently, inhibitors of class I and class II HDAC have been successfully employed for the treatment of different inflammatory diseases such as rheumatoid arthritis, colitis, airway inflammation and asthma. So f...

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Main Authors: Orecchia, Angela, Scarponi, Claudia, Di Felice, Francesca, Cesarini, Elisa, Avitabile, Simona, Mai, Antonello, Mauro, Maria Luisa, Sirri, Valentina, Zambruno, Giovanna, Albanesi, Cristina, Camilloni, Giorgio, Failla, Cristina M.
Format: Online
Language:English
Published: Public Library of Science 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171404/
id pubmed-3171404
recordtype oai_dc
spelling pubmed-31714042011-09-19 Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells Orecchia, Angela Scarponi, Claudia Di Felice, Francesca Cesarini, Elisa Avitabile, Simona Mai, Antonello Mauro, Maria Luisa Sirri, Valentina Zambruno, Giovanna Albanesi, Cristina Camilloni, Giorgio Failla, Cristina M. Research Article Histone deacetylases (HDAC) are key enzymes in the epigenetic control of gene expression. Recently, inhibitors of class I and class II HDAC have been successfully employed for the treatment of different inflammatory diseases such as rheumatoid arthritis, colitis, airway inflammation and asthma. So far, little is known so far about a similar therapeutic effect of inhibitors specifically directed against sirtuins, the class III HDAC. In this study, we investigated the expression and localization of endogenous sirtuins in primary human dermal microvascular endothelial cells (HDMEC), a cell type playing a key role in the development and maintenance of skin inflammation. We then examined the biological activity of sirtinol, a specific sirtuin inhibitor, in HDMEC response to pro-inflammatory cytokines. We found that, even though sirtinol treatment alone affected only long-term cell proliferation, it diminishes HDMEC inflammatory responses to tumor necrosis factor (TNF)α and interleukin (IL)-1β. In fact, sirtinol significantly reduced membrane expression of adhesion molecules in TNFã- or IL-1β-stimulated cells, as well as the amount of CXCL10 and CCL2 released by HDMEC following TNFα treatment. Notably, sirtinol drastically decreased monocyte adhesion on activated HDMEC. Using selective inhibitors for Sirt1 and Sirt2, we showed a predominant involvement of Sirt1 inhibition in the modulation of adhesion molecule expression and monocyte adhesion on activated HDMEC. Finally, we demonstrated the in vivo expression of Sirt1 in the dermal vessels of normal and psoriatic skin. Altogether, these findings indicated that sirtuins may represent a promising therapeutic target for the treatment of inflammatory skin diseases characterized by a prominent microvessel involvement. Public Library of Science 2011-09-12 /pmc/articles/PMC3171404/ /pubmed/21931678 http://dx.doi.org/10.1371/journal.pone.0024307 Text en Orecchia et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Orecchia, Angela
Scarponi, Claudia
Di Felice, Francesca
Cesarini, Elisa
Avitabile, Simona
Mai, Antonello
Mauro, Maria Luisa
Sirri, Valentina
Zambruno, Giovanna
Albanesi, Cristina
Camilloni, Giorgio
Failla, Cristina M.
spellingShingle Orecchia, Angela
Scarponi, Claudia
Di Felice, Francesca
Cesarini, Elisa
Avitabile, Simona
Mai, Antonello
Mauro, Maria Luisa
Sirri, Valentina
Zambruno, Giovanna
Albanesi, Cristina
Camilloni, Giorgio
Failla, Cristina M.
Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells
author_facet Orecchia, Angela
Scarponi, Claudia
Di Felice, Francesca
Cesarini, Elisa
Avitabile, Simona
Mai, Antonello
Mauro, Maria Luisa
Sirri, Valentina
Zambruno, Giovanna
Albanesi, Cristina
Camilloni, Giorgio
Failla, Cristina M.
author_sort Orecchia, Angela
title Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells
title_short Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells
title_full Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells
title_fullStr Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells
title_full_unstemmed Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells
title_sort sirtinol treatment reduces inflammation in human dermal microvascular endothelial cells
description Histone deacetylases (HDAC) are key enzymes in the epigenetic control of gene expression. Recently, inhibitors of class I and class II HDAC have been successfully employed for the treatment of different inflammatory diseases such as rheumatoid arthritis, colitis, airway inflammation and asthma. So far, little is known so far about a similar therapeutic effect of inhibitors specifically directed against sirtuins, the class III HDAC. In this study, we investigated the expression and localization of endogenous sirtuins in primary human dermal microvascular endothelial cells (HDMEC), a cell type playing a key role in the development and maintenance of skin inflammation. We then examined the biological activity of sirtinol, a specific sirtuin inhibitor, in HDMEC response to pro-inflammatory cytokines. We found that, even though sirtinol treatment alone affected only long-term cell proliferation, it diminishes HDMEC inflammatory responses to tumor necrosis factor (TNF)α and interleukin (IL)-1β. In fact, sirtinol significantly reduced membrane expression of adhesion molecules in TNFã- or IL-1β-stimulated cells, as well as the amount of CXCL10 and CCL2 released by HDMEC following TNFα treatment. Notably, sirtinol drastically decreased monocyte adhesion on activated HDMEC. Using selective inhibitors for Sirt1 and Sirt2, we showed a predominant involvement of Sirt1 inhibition in the modulation of adhesion molecule expression and monocyte adhesion on activated HDMEC. Finally, we demonstrated the in vivo expression of Sirt1 in the dermal vessels of normal and psoriatic skin. Altogether, these findings indicated that sirtuins may represent a promising therapeutic target for the treatment of inflammatory skin diseases characterized by a prominent microvessel involvement.
publisher Public Library of Science
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171404/
_version_ 1611475166549770240

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