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The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association
We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 ± 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 µl) or lipopolysaccharide (LPS) (1 mg/kg in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374436/ https://www.ncbi.nlm.nih.gov/pubmed/30760822 http://dx.doi.org/10.1038/s41598-019-38600-z |
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author | Cervilha, Daniela A. B. Ito, Juliana T. Lourenço, Juliana D. Olivo, Clarice R. Saraiva-Romanholo, Beatriz M. Volpini, Rildo A. Oliveira-Junior, Manoel C. Mauad, Thais Martins, Milton A. Tibério, Iolanda F. L. C. Vieira, Rodolfo P. Lopes, Fernanda D. T. Q. S. |
author_facet | Cervilha, Daniela A. B. Ito, Juliana T. Lourenço, Juliana D. Olivo, Clarice R. Saraiva-Romanholo, Beatriz M. Volpini, Rildo A. Oliveira-Junior, Manoel C. Mauad, Thais Martins, Milton A. Tibério, Iolanda F. L. C. Vieira, Rodolfo P. Lopes, Fernanda D. T. Q. S. |
author_sort | Cervilha, Daniela A. B. |
collection | PubMed |
description | We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 ± 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 µl) or lipopolysaccharide (LPS) (1 mg/kg in 50 µl of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4(+) and CD8(+) T cells, Treg cells, and IL-10(+) and IL-17(+) cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-γ, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4(+) and CD8(+) T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17(+) cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5(+) cells corroborated the increased numbers of IL-17(+) and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL-10(+) cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model. |
format | Online Article Text |
id | pubmed-6374436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63744362019-02-19 The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association Cervilha, Daniela A. B. Ito, Juliana T. Lourenço, Juliana D. Olivo, Clarice R. Saraiva-Romanholo, Beatriz M. Volpini, Rildo A. Oliveira-Junior, Manoel C. Mauad, Thais Martins, Milton A. Tibério, Iolanda F. L. C. Vieira, Rodolfo P. Lopes, Fernanda D. T. Q. S. Sci Rep Article We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 ± 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 µl) or lipopolysaccharide (LPS) (1 mg/kg in 50 µl of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4(+) and CD8(+) T cells, Treg cells, and IL-10(+) and IL-17(+) cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-γ, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4(+) and CD8(+) T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17(+) cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5(+) cells corroborated the increased numbers of IL-17(+) and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL-10(+) cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model. Nature Publishing Group UK 2019-02-13 /pmc/articles/PMC6374436/ /pubmed/30760822 http://dx.doi.org/10.1038/s41598-019-38600-z 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 Cervilha, Daniela A. B. Ito, Juliana T. Lourenço, Juliana D. Olivo, Clarice R. Saraiva-Romanholo, Beatriz M. Volpini, Rildo A. Oliveira-Junior, Manoel C. Mauad, Thais Martins, Milton A. Tibério, Iolanda F. L. C. Vieira, Rodolfo P. Lopes, Fernanda D. T. Q. S. The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association |
title | The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association |
title_full | The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association |
title_fullStr | The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association |
title_full_unstemmed | The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association |
title_short | The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association |
title_sort | th17/treg cytokine imbalance in chronic obstructive pulmonary disease exacerbation in an animal model of cigarette smoke exposure and lipopolysaccharide challenge association |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374436/ https://www.ncbi.nlm.nih.gov/pubmed/30760822 http://dx.doi.org/10.1038/s41598-019-38600-z |
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