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Losartan does not inhibit cigarette smoke-induced lung inflammation in mice
Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease largely caused by cigarette smoking (CS) and is characterized by lung inflammation and airflow limitation that is not fully reversible. Approximately 50% of people with COPD die of a cardiovascular comorbidity and current pha...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803700/ https://www.ncbi.nlm.nih.gov/pubmed/31636311 http://dx.doi.org/10.1038/s41598-019-51504-2 |
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author | Hepworth, M. L. Passey, S. L. Seow, H. J. Vlahos, R. |
author_facet | Hepworth, M. L. Passey, S. L. Seow, H. J. Vlahos, R. |
author_sort | Hepworth, M. L. |
collection | PubMed |
description | Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease largely caused by cigarette smoking (CS) and is characterized by lung inflammation and airflow limitation that is not fully reversible. Approximately 50% of people with COPD die of a cardiovascular comorbidity and current pharmacological strategies provide little benefit. Therefore, drugs that target the lung and the cardiovascular system concurrently may be an advantageous therapeutic strategy. The aim of this study was to see whether losartan, an angiotensin-II AT1a receptor antagonist widely used to treat hypertension associated with cardiovascular disease, protects against CS-induced lung inflammation in mice. Male BALB/c mice were exposed to CS for 8 weeks and treated with either losartan (30 mg/kg) or vehicle daily. Mice were euthanized and bronchoalveolar lavage fluid (BALF) inflammation, and whole lung cytokine, chemokine and protease mRNA expression assessed. CS caused significant increases in BALF total cells, macrophages, neutrophils and whole lung IL-6, TNF-α, CXCL-1, IL-17A and MMP12 mRNA expression compared to sham-exposed mice. However, losartan only reduced CS-induced increases in IL-6 mRNA expression. Angiotensin-II receptor expression was reduced in lung tissue from CS-exposed mice. In conclusion, losartan did not inhibit CS-induced BALF cellularity despite reducing whole lung IL-6 mRNA and Ang-II receptor expression. |
format | Online Article Text |
id | pubmed-6803700 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68037002019-10-24 Losartan does not inhibit cigarette smoke-induced lung inflammation in mice Hepworth, M. L. Passey, S. L. Seow, H. J. Vlahos, R. Sci Rep Article Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease largely caused by cigarette smoking (CS) and is characterized by lung inflammation and airflow limitation that is not fully reversible. Approximately 50% of people with COPD die of a cardiovascular comorbidity and current pharmacological strategies provide little benefit. Therefore, drugs that target the lung and the cardiovascular system concurrently may be an advantageous therapeutic strategy. The aim of this study was to see whether losartan, an angiotensin-II AT1a receptor antagonist widely used to treat hypertension associated with cardiovascular disease, protects against CS-induced lung inflammation in mice. Male BALB/c mice were exposed to CS for 8 weeks and treated with either losartan (30 mg/kg) or vehicle daily. Mice were euthanized and bronchoalveolar lavage fluid (BALF) inflammation, and whole lung cytokine, chemokine and protease mRNA expression assessed. CS caused significant increases in BALF total cells, macrophages, neutrophils and whole lung IL-6, TNF-α, CXCL-1, IL-17A and MMP12 mRNA expression compared to sham-exposed mice. However, losartan only reduced CS-induced increases in IL-6 mRNA expression. Angiotensin-II receptor expression was reduced in lung tissue from CS-exposed mice. In conclusion, losartan did not inhibit CS-induced BALF cellularity despite reducing whole lung IL-6 mRNA and Ang-II receptor expression. Nature Publishing Group UK 2019-10-21 /pmc/articles/PMC6803700/ /pubmed/31636311 http://dx.doi.org/10.1038/s41598-019-51504-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hepworth, M. L. Passey, S. L. Seow, H. J. Vlahos, R. Losartan does not inhibit cigarette smoke-induced lung inflammation in mice |
title | Losartan does not inhibit cigarette smoke-induced lung inflammation in mice |
title_full | Losartan does not inhibit cigarette smoke-induced lung inflammation in mice |
title_fullStr | Losartan does not inhibit cigarette smoke-induced lung inflammation in mice |
title_full_unstemmed | Losartan does not inhibit cigarette smoke-induced lung inflammation in mice |
title_short | Losartan does not inhibit cigarette smoke-induced lung inflammation in mice |
title_sort | losartan does not inhibit cigarette smoke-induced lung inflammation in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803700/ https://www.ncbi.nlm.nih.gov/pubmed/31636311 http://dx.doi.org/10.1038/s41598-019-51504-2 |
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