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Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammat...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2959025/ https://www.ncbi.nlm.nih.gov/pubmed/20920344 http://dx.doi.org/10.1186/1465-9921-11-134 |
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author | Pauwels, Nele S Bracke, Ken R Maes, Tania Van Pottelberge, Geert R Garlanda, Cecilia Mantovani, Alberto Joos, Guy F Brusselle, Guy G |
author_facet | Pauwels, Nele S Bracke, Ken R Maes, Tania Van Pottelberge, Geert R Garlanda, Cecilia Mantovani, Alberto Joos, Guy F Brusselle, Guy G |
author_sort | Pauwels, Nele S |
collection | PubMed |
description | BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammatory cells upon stimuli such as interleukin-1β (IL-1β), we hypothesized that PTX3 is involved in COPD pathogenesis. METHODS AND RESULTS: We evaluated whether cigarette smoke (CS) triggers pulmonary and systemic PTX3 expression in vivo in a murine model of COPD. Using immunohistochemical (IHC) staining, we observed PTX3 expression in endothelial cells of lung venules and veins but not in lung arteries, airways and parenchyma. Moreover, ELISA on lung homogenates and semi-quantitative scoring of IHC-stained sections revealed a significant upregulation of PTX3 upon subacute and chronic CS exposure. Interestingly, PTX3 expression was not enhanced upon subacute CS exposure in IL-1RI KO mice, suggesting that the IL-1 pathway is implicated in CS-induced expression of vascular PTX3. Serum PTX3 levels increased rapidly but transiently after acute CS exposure. To elucidate the functional role of PTX3 in CS-induced responses, we examined pulmonary inflammation, protease/antiprotease balance, emphysema and body weight changes in WT and Ptx3 KO mice. CS-induced pulmonary inflammation, peribronchial lymphoid aggregates, increase in MMP-12/TIMP-1 mRNA ratio, emphysema and failure to gain weight were not significantly different in Ptx3 KO mice compared to WT mice. In addition, Ptx3 deficiency did not affect the CS-induced alterations in the pulmonary (mRNA and protein) expression of VEGF-A and FGF-2, which are crucial regulators of angiogenesis. CONCLUSIONS: CS increases pulmonary PTX3 expression in an IL-1 dependent manner. However, our results suggest that either PTX3 is not critical in CS-induced pulmonary inflammation, emphysema and body weight changes, or that its role can be fulfilled by other mediators with overlapping activities. |
format | Text |
id | pubmed-2959025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29590252010-10-22 Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner Pauwels, Nele S Bracke, Ken R Maes, Tania Van Pottelberge, Geert R Garlanda, Cecilia Mantovani, Alberto Joos, Guy F Brusselle, Guy G Respir Res Research BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammatory cells upon stimuli such as interleukin-1β (IL-1β), we hypothesized that PTX3 is involved in COPD pathogenesis. METHODS AND RESULTS: We evaluated whether cigarette smoke (CS) triggers pulmonary and systemic PTX3 expression in vivo in a murine model of COPD. Using immunohistochemical (IHC) staining, we observed PTX3 expression in endothelial cells of lung venules and veins but not in lung arteries, airways and parenchyma. Moreover, ELISA on lung homogenates and semi-quantitative scoring of IHC-stained sections revealed a significant upregulation of PTX3 upon subacute and chronic CS exposure. Interestingly, PTX3 expression was not enhanced upon subacute CS exposure in IL-1RI KO mice, suggesting that the IL-1 pathway is implicated in CS-induced expression of vascular PTX3. Serum PTX3 levels increased rapidly but transiently after acute CS exposure. To elucidate the functional role of PTX3 in CS-induced responses, we examined pulmonary inflammation, protease/antiprotease balance, emphysema and body weight changes in WT and Ptx3 KO mice. CS-induced pulmonary inflammation, peribronchial lymphoid aggregates, increase in MMP-12/TIMP-1 mRNA ratio, emphysema and failure to gain weight were not significantly different in Ptx3 KO mice compared to WT mice. In addition, Ptx3 deficiency did not affect the CS-induced alterations in the pulmonary (mRNA and protein) expression of VEGF-A and FGF-2, which are crucial regulators of angiogenesis. CONCLUSIONS: CS increases pulmonary PTX3 expression in an IL-1 dependent manner. However, our results suggest that either PTX3 is not critical in CS-induced pulmonary inflammation, emphysema and body weight changes, or that its role can be fulfilled by other mediators with overlapping activities. BioMed Central 2010 2010-10-04 /pmc/articles/PMC2959025/ /pubmed/20920344 http://dx.doi.org/10.1186/1465-9921-11-134 Text en Copyright ©2010 Pauwels et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Pauwels, Nele S Bracke, Ken R Maes, Tania Van Pottelberge, Geert R Garlanda, Cecilia Mantovani, Alberto Joos, Guy F Brusselle, Guy G Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner |
title | Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner |
title_full | Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner |
title_fullStr | Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner |
title_full_unstemmed | Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner |
title_short | Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner |
title_sort | cigarette smoke induces ptx3 expression in pulmonary veins of mice in an il-1 dependent manner |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2959025/ https://www.ncbi.nlm.nih.gov/pubmed/20920344 http://dx.doi.org/10.1186/1465-9921-11-134 |
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