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Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice

BACKGROUND: Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity. OBJECTIVES: We determined the immunotoxic potential of Dec 602 in mice by ex...

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Autores principales: Feng, Yu, Tian, Jijing, Xie, Heidi Qunhui, She, Jianwen, Xu, Sherry Li, Xu, Tuan, Tian, Wenjing, Fu, Hualing, Li, Shuaizhang, Tao, Wuqun, Wang, Lingyun, Chen, Yangsheng, Zhang, Songyan, Zhang, Wanglong, Guo, Tai L., Zhao, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010418/
https://www.ncbi.nlm.nih.gov/pubmed/27081854
http://dx.doi.org/10.1289/ehp.1510314
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author Feng, Yu
Tian, Jijing
Xie, Heidi Qunhui
She, Jianwen
Xu, Sherry Li
Xu, Tuan
Tian, Wenjing
Fu, Hualing
Li, Shuaizhang
Tao, Wuqun
Wang, Lingyun
Chen, Yangsheng
Zhang, Songyan
Zhang, Wanglong
Guo, Tai L.
Zhao, Bin
author_facet Feng, Yu
Tian, Jijing
Xie, Heidi Qunhui
She, Jianwen
Xu, Sherry Li
Xu, Tuan
Tian, Wenjing
Fu, Hualing
Li, Shuaizhang
Tao, Wuqun
Wang, Lingyun
Chen, Yangsheng
Zhang, Songyan
Zhang, Wanglong
Guo, Tai L.
Zhao, Bin
author_sort Feng, Yu
collection PubMed
description BACKGROUND: Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity. OBJECTIVES: We determined the immunotoxic potential of Dec 602 in mice by examining the expression of phenotypic markers on thymocyte and splenic lymphocyte subsets, Th1/Th2 transcription factors, and the production of cytokines and antibodies. METHODS: Adult male C57BL/6 mice were orally exposed to environmentally relevant doses of Dec 602 (1 and 10 μg/kg body weight per day) for 7 consecutive days. Thymocyte and splenic CD4 and CD8 subsets and splenocyte apoptosis were examined by flow cytometric analysis. Cytokine expression was measured at both the mRNA and the protein levels. Levels of the transcription factors Th1 (T-bet and STAT1) and Th2 (GATA3) were determined using quantitative real-time polymerase chain reaction (qPCR). Serum levels of immunoglobulins IgG1, IgG2a, IgG2b and IgE were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Splenic CD4+ and CD8+ T cell subsets were decreased compared with vehicle controls, and apoptosis was significantly increased in splenic CD4+ T cells. Expression (mRNA and protein) of Th2 cytokines [interleukin (IL)-4, IL-10, and IL-13] increased, and that of Th1 cytokines [IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] decreased. The Th2 transcriptional factor GATA3 increased, whereas the Th1 transcriptional factors T-bet and STAT1 decreased. As additional indicators of the Th2-Th1 imbalance, production of IgG1 was significantly increased, whereas IgG2a was reduced. CONCLUSIONS: To our knowledge, we are the first to report evidence of the effects of Dec 602 on immune function in mice, with findings indicating that Dec 602 exposure favored Th2 responses and reduced Th1 function. CITATION: Feng Y, Tian J, Xie HQ, She J, Xu SL, Xu T, Tian W, Fu H, Li S, Tao W, Wang L, Chen Y, Zhang S, Zhang W, Guo TL, Zhao B. 2016. Effects of acute low-dose exposure to the chlorinated flame retardant dechlorane 602 and Th1 and Th2 immune responses in adult male mice. Environ Health Perspect 124:1406–1413; http://dx.doi.org/10.1289/ehp.1510314
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spelling pubmed-50104182016-09-13 Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice Feng, Yu Tian, Jijing Xie, Heidi Qunhui She, Jianwen Xu, Sherry Li Xu, Tuan Tian, Wenjing Fu, Hualing Li, Shuaizhang Tao, Wuqun Wang, Lingyun Chen, Yangsheng Zhang, Songyan Zhang, Wanglong Guo, Tai L. Zhao, Bin Environ Health Perspect Research BACKGROUND: Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity. OBJECTIVES: We determined the immunotoxic potential of Dec 602 in mice by examining the expression of phenotypic markers on thymocyte and splenic lymphocyte subsets, Th1/Th2 transcription factors, and the production of cytokines and antibodies. METHODS: Adult male C57BL/6 mice were orally exposed to environmentally relevant doses of Dec 602 (1 and 10 μg/kg body weight per day) for 7 consecutive days. Thymocyte and splenic CD4 and CD8 subsets and splenocyte apoptosis were examined by flow cytometric analysis. Cytokine expression was measured at both the mRNA and the protein levels. Levels of the transcription factors Th1 (T-bet and STAT1) and Th2 (GATA3) were determined using quantitative real-time polymerase chain reaction (qPCR). Serum levels of immunoglobulins IgG1, IgG2a, IgG2b and IgE were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Splenic CD4+ and CD8+ T cell subsets were decreased compared with vehicle controls, and apoptosis was significantly increased in splenic CD4+ T cells. Expression (mRNA and protein) of Th2 cytokines [interleukin (IL)-4, IL-10, and IL-13] increased, and that of Th1 cytokines [IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] decreased. The Th2 transcriptional factor GATA3 increased, whereas the Th1 transcriptional factors T-bet and STAT1 decreased. As additional indicators of the Th2-Th1 imbalance, production of IgG1 was significantly increased, whereas IgG2a was reduced. CONCLUSIONS: To our knowledge, we are the first to report evidence of the effects of Dec 602 on immune function in mice, with findings indicating that Dec 602 exposure favored Th2 responses and reduced Th1 function. CITATION: Feng Y, Tian J, Xie HQ, She J, Xu SL, Xu T, Tian W, Fu H, Li S, Tao W, Wang L, Chen Y, Zhang S, Zhang W, Guo TL, Zhao B. 2016. Effects of acute low-dose exposure to the chlorinated flame retardant dechlorane 602 and Th1 and Th2 immune responses in adult male mice. Environ Health Perspect 124:1406–1413; http://dx.doi.org/10.1289/ehp.1510314 National Institute of Environmental Health Sciences 2016-04-15 2016-09 /pmc/articles/PMC5010418/ /pubmed/27081854 http://dx.doi.org/10.1289/ehp.1510314 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Feng, Yu
Tian, Jijing
Xie, Heidi Qunhui
She, Jianwen
Xu, Sherry Li
Xu, Tuan
Tian, Wenjing
Fu, Hualing
Li, Shuaizhang
Tao, Wuqun
Wang, Lingyun
Chen, Yangsheng
Zhang, Songyan
Zhang, Wanglong
Guo, Tai L.
Zhao, Bin
Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice
title Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice
title_full Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice
title_fullStr Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice
title_full_unstemmed Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice
title_short Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice
title_sort effects of acute low-dose exposure to the chlorinated flame retardant dechlorane 602 and th1 and th2 immune responses in adult male mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010418/
https://www.ncbi.nlm.nih.gov/pubmed/27081854
http://dx.doi.org/10.1289/ehp.1510314
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