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Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages
BACKGROUND: Alcohol abuse is involved in the pathogenesis of multiple organ disorders; the underlying mechanism is incompletely understood. The ubiquitin editing enzyme A20 is involved in regulating activities in the cell. Suppression of A20 is suggested as one factor in the initiation of inflammati...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436623/ https://www.ncbi.nlm.nih.gov/pubmed/22958952 http://dx.doi.org/10.1186/2049-6958-6-6-364 |
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author | Huang, Quan-Yong Chen, Yu-Chuan Liu, Shui-Ping |
author_facet | Huang, Quan-Yong Chen, Yu-Chuan Liu, Shui-Ping |
author_sort | Huang, Quan-Yong |
collection | PubMed |
description | BACKGROUND: Alcohol abuse is involved in the pathogenesis of multiple organ disorders; the underlying mechanism is incompletely understood. The ubiquitin editing enzyme A20 is involved in regulating activities in the cell. Suppression of A20 is suggested as one factor in the initiation of inflammation. This study investigates the mechanism by which chronic alcohol consumption modulates the levels of ubiquitin editing enzyme A20 in macrophages and further contributes to induce endothelial barrier dysfunction in the lung. METHODS: Mice were gavage-fed with 40% alcohol daily for 0-3 weeks. Airway macrophages were collected by lung lavage. Expression of ubiquitin editing enzyme A20 in isolated macrophages was assessed at both mRNA and protein levels. The endothelial barrier function of the lung was evaluated by the Evans blue method. RESULTS: Mice treated with alcohol for 3 weeks showed an increase in cell infiltration in the lung in response to exposure to peptidoglycan; over 80% of the infiltrated cells were macrophages. Furthermore, we observed that A20 level was suppressed in macrophages of mice treated with alcohol; the levels of tumor necrosis factor, interleukin-6 and nuclear factor kappa B in macrophage were increased. In addition, the endothelial barrier function of the lung was compromised, showing excessive infiltration of Evans blue in the lung indicating lung edema. Pretreatment with synthesized A20 inhibited alcohol-induced lung endothelial barrier dysfunction. CONCLUSIONS: We conclude that chronic alcohol ingestion disturbs the endothelial barrier function in the lung by modulating macrophage properties. Increase in A20 in the cell may have potential for the treatment of inflammatory disorders. |
format | Online Article Text |
id | pubmed-3436623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34366232012-09-08 Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages Huang, Quan-Yong Chen, Yu-Chuan Liu, Shui-Ping Multidiscip Respir Med Original Article BACKGROUND: Alcohol abuse is involved in the pathogenesis of multiple organ disorders; the underlying mechanism is incompletely understood. The ubiquitin editing enzyme A20 is involved in regulating activities in the cell. Suppression of A20 is suggested as one factor in the initiation of inflammation. This study investigates the mechanism by which chronic alcohol consumption modulates the levels of ubiquitin editing enzyme A20 in macrophages and further contributes to induce endothelial barrier dysfunction in the lung. METHODS: Mice were gavage-fed with 40% alcohol daily for 0-3 weeks. Airway macrophages were collected by lung lavage. Expression of ubiquitin editing enzyme A20 in isolated macrophages was assessed at both mRNA and protein levels. The endothelial barrier function of the lung was evaluated by the Evans blue method. RESULTS: Mice treated with alcohol for 3 weeks showed an increase in cell infiltration in the lung in response to exposure to peptidoglycan; over 80% of the infiltrated cells were macrophages. Furthermore, we observed that A20 level was suppressed in macrophages of mice treated with alcohol; the levels of tumor necrosis factor, interleukin-6 and nuclear factor kappa B in macrophage were increased. In addition, the endothelial barrier function of the lung was compromised, showing excessive infiltration of Evans blue in the lung indicating lung edema. Pretreatment with synthesized A20 inhibited alcohol-induced lung endothelial barrier dysfunction. CONCLUSIONS: We conclude that chronic alcohol ingestion disturbs the endothelial barrier function in the lung by modulating macrophage properties. Increase in A20 in the cell may have potential for the treatment of inflammatory disorders. BioMed Central 2011-12-20 /pmc/articles/PMC3436623/ /pubmed/22958952 http://dx.doi.org/10.1186/2049-6958-6-6-364 Text en Copyright ©2011 Novamedia srl |
spellingShingle | Original Article Huang, Quan-Yong Chen, Yu-Chuan Liu, Shui-Ping Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages |
title | Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages |
title_full | Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages |
title_fullStr | Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages |
title_full_unstemmed | Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages |
title_short | Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages |
title_sort | chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme a20 in lung macrophages |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436623/ https://www.ncbi.nlm.nih.gov/pubmed/22958952 http://dx.doi.org/10.1186/2049-6958-6-6-364 |
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