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Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development
BACKGROUND: COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598950/ https://www.ncbi.nlm.nih.gov/pubmed/28910300 http://dx.doi.org/10.1371/journal.pone.0183741 |
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author | Khedoe, P. Padmini S. J. de Kleijn, Stan van Oeveren-Rietdijk, Annemarie M. Plomp, Jaap J. de Boer, Hetty C. van Pel, Melissa Rensen, Patrick C. N. Berbée, Jimmy F. P. Hiemstra, Pieter S. |
author_facet | Khedoe, P. Padmini S. J. de Kleijn, Stan van Oeveren-Rietdijk, Annemarie M. Plomp, Jaap J. de Boer, Hetty C. van Pel, Melissa Rensen, Patrick C. N. Berbée, Jimmy F. P. Hiemstra, Pieter S. |
author_sort | Khedoe, P. Padmini S. J. |
collection | PubMed |
description | BACKGROUND: COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice. METHODS: Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x10(6) MSC or vehicle intravenously twice after the first LPS instillation (acute study) or in week 14, 16, 18 and 20 (chronic study). Inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study. RESULTS: In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment. CONCLUSION: These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study. |
format | Online Article Text |
id | pubmed-5598950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55989502017-09-22 Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development Khedoe, P. Padmini S. J. de Kleijn, Stan van Oeveren-Rietdijk, Annemarie M. Plomp, Jaap J. de Boer, Hetty C. van Pel, Melissa Rensen, Patrick C. N. Berbée, Jimmy F. P. Hiemstra, Pieter S. PLoS One Research Article BACKGROUND: COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice. METHODS: Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x10(6) MSC or vehicle intravenously twice after the first LPS instillation (acute study) or in week 14, 16, 18 and 20 (chronic study). Inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study. RESULTS: In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment. CONCLUSION: These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study. Public Library of Science 2017-09-14 /pmc/articles/PMC5598950/ /pubmed/28910300 http://dx.doi.org/10.1371/journal.pone.0183741 Text en © 2017 Khedoe 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Khedoe, P. Padmini S. J. de Kleijn, Stan van Oeveren-Rietdijk, Annemarie M. Plomp, Jaap J. de Boer, Hetty C. van Pel, Melissa Rensen, Patrick C. N. Berbée, Jimmy F. P. Hiemstra, Pieter S. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development |
title | Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development |
title_full | Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development |
title_fullStr | Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development |
title_full_unstemmed | Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development |
title_short | Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development |
title_sort | acute and chronic effects of treatment with mesenchymal stromal cells on lps-induced pulmonary inflammation, emphysema and atherosclerosis development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598950/ https://www.ncbi.nlm.nih.gov/pubmed/28910300 http://dx.doi.org/10.1371/journal.pone.0183741 |
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