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Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity
Lung fibrosis may be associated with Type-2 polarized inflammation. Herein, we aim to investigate whether radiation can initiate a Type-2 immune response and contribute to the progression of pulmonary fibrosis in tumor-bearing animals. We developed a tumor-bearing mouse model with Lewis lung cancer...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795947/ https://www.ncbi.nlm.nih.gov/pubmed/26703457 http://dx.doi.org/10.1093/jrr/rrv077 |
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author | Chen, Jing Wang, Yacheng Mei, Zijie Zhang, Shimin Yang, Jie Li, Xin Yao, Ye Xie, Conghua |
author_facet | Chen, Jing Wang, Yacheng Mei, Zijie Zhang, Shimin Yang, Jie Li, Xin Yao, Ye Xie, Conghua |
author_sort | Chen, Jing |
collection | PubMed |
description | Lung fibrosis may be associated with Type-2 polarized inflammation. Herein, we aim to investigate whether radiation can initiate a Type-2 immune response and contribute to the progression of pulmonary fibrosis in tumor-bearing animals. We developed a tumor-bearing mouse model with Lewis lung cancer to receive either radiation therapy alone or radiation combined with Th1 immunomodulator unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotide (CpG-ODN). The Type-2 immune phenotype in tumors and the histological grade of lung fibrosis were evaluated in mice sacrificed three weeks after irradiation. Mouse lung tissues were analyzed for hydroxyproline and the expression of Type-1/Type-2 key transcription factors (T-bet/GATA-3). The concentration of Type-1/Type-2 cytokines in serum was measured by cytometric bead array. Lung fibrosis was observed to be more serious in tumor-bearing mice than in normal mice post-irradiation. The fibrosis score in irradiated tumor-bearing mice on Day 21 was 4.33 ± 0.82, which was higher than that of normal mice (2.00 ± 0.63; P < 0.05). Hydroxyproline and GATA-3 expression were increased in the lung tissues of tumor-bearing mice following irradiation. CpG-ODN attenuated fibrosis by markedly decreasing GATA-3 expression. Serum IL-13 and IL-5 were elevated, whereas INF-γ and IL-12 expression were decreased in irradiated tumor-bearing mice. These changes were reversed after CpG-ODN treatment. Thus, Type-2 immunity in tumors appeared to affect the outcome of radiation damage and might be of interest for future studies on developing approaches in which Type-1–related immunotherapy and radiotherapy are used in combination. |
format | Online Article Text |
id | pubmed-4795947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47959472016-03-21 Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity Chen, Jing Wang, Yacheng Mei, Zijie Zhang, Shimin Yang, Jie Li, Xin Yao, Ye Xie, Conghua J Radiat Res Biology Lung fibrosis may be associated with Type-2 polarized inflammation. Herein, we aim to investigate whether radiation can initiate a Type-2 immune response and contribute to the progression of pulmonary fibrosis in tumor-bearing animals. We developed a tumor-bearing mouse model with Lewis lung cancer to receive either radiation therapy alone or radiation combined with Th1 immunomodulator unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotide (CpG-ODN). The Type-2 immune phenotype in tumors and the histological grade of lung fibrosis were evaluated in mice sacrificed three weeks after irradiation. Mouse lung tissues were analyzed for hydroxyproline and the expression of Type-1/Type-2 key transcription factors (T-bet/GATA-3). The concentration of Type-1/Type-2 cytokines in serum was measured by cytometric bead array. Lung fibrosis was observed to be more serious in tumor-bearing mice than in normal mice post-irradiation. The fibrosis score in irradiated tumor-bearing mice on Day 21 was 4.33 ± 0.82, which was higher than that of normal mice (2.00 ± 0.63; P < 0.05). Hydroxyproline and GATA-3 expression were increased in the lung tissues of tumor-bearing mice following irradiation. CpG-ODN attenuated fibrosis by markedly decreasing GATA-3 expression. Serum IL-13 and IL-5 were elevated, whereas INF-γ and IL-12 expression were decreased in irradiated tumor-bearing mice. These changes were reversed after CpG-ODN treatment. Thus, Type-2 immunity in tumors appeared to affect the outcome of radiation damage and might be of interest for future studies on developing approaches in which Type-1–related immunotherapy and radiotherapy are used in combination. Oxford University Press 2016-03 2015-12-24 /pmc/articles/PMC4795947/ /pubmed/26703457 http://dx.doi.org/10.1093/jrr/rrv077 Text en © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Biology Chen, Jing Wang, Yacheng Mei, Zijie Zhang, Shimin Yang, Jie Li, Xin Yao, Ye Xie, Conghua Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity |
title | Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity |
title_full | Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity |
title_fullStr | Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity |
title_full_unstemmed | Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity |
title_short | Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity |
title_sort | radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced type-2 immunity |
topic | Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795947/ https://www.ncbi.nlm.nih.gov/pubmed/26703457 http://dx.doi.org/10.1093/jrr/rrv077 |
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