Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage
Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macro...
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Elsevier
2021-06-01
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Series: | Ecotoxicology and Environmental Safety |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321002396 |
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author | Jinglin Tian Yanjun Hong Zhenchi Li Zhiyi Yang Bo Lei Jianjun Liu Zongwei Cai |
author_facet | Jinglin Tian Yanjun Hong Zhenchi Li Zhiyi Yang Bo Lei Jianjun Liu Zongwei Cai |
author_sort | Jinglin Tian |
collection | DOAJ |
description | Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macrophage RAW264.7. We assessed the effects of PFOA exposure on macrophage cell viability, cell apoptosis and cellular ROS level, and detected prominent cytokines release by RAW264.7. The results indicated that the cell viability of macrophage RAW264.7 was decreased by PFOA in dose- and time-dependent manners. Specifically, the exposure of 200 μM PFOA significantly increased apoptosis and ROS generation in macrophage, and thus caused cell damage. The ELISA results displayed that 100 μM PFOA exposure induced macrophage activation and enhanced cytokines secretion, including TNF-α, IL-1, IL-6, and IL-12. We also conducted nontargeted metabolomics based on LC-MS/MS and unveiled the perturbed metabolic pathways in macrophages induced by sublethal doses of PFOA (10 μM and 100 μM). Remarkably, global metabolomics results displayed that 10 μM PFOA exposure affected glutamine related pathways and the exposure at 100 μM conspicuously changed glutathione and fatty acid oxidation metabolism. These findings showed that 10 μM PFOA exposure could impel metabolic reprogramming of macrophage to trigger inflammatory response, although such dose displayed no obvious effect on cell viability, cellular ROS or apoptosis events of macrophage RAW264.7. |
first_indexed | 2024-12-14T17:29:39Z |
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institution | Directory Open Access Journal |
issn | 0147-6513 |
language | English |
last_indexed | 2024-12-14T17:29:39Z |
publishDate | 2021-06-01 |
publisher | Elsevier |
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series | Ecotoxicology and Environmental Safety |
spelling | doaj.art-a7c91a5622ed40348edb36422c443f9b2022-12-21T22:53:09ZengElsevierEcotoxicology and Environmental Safety0147-65132021-06-01215112128Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophageJinglin Tian0Yanjun Hong1Zhenchi Li2Zhiyi Yang3Bo Lei4Jianjun Liu5Zongwei Cai6Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, ChinaState Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, China; Corresponding author at: School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, China.Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, ChinaState Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaFood Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, ChinaShenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen, China; Correspondence to: Shenzhen Center for Disease Control and Prevention, Shenzhen, China.Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; Corresponding author at: Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China.Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macrophage RAW264.7. We assessed the effects of PFOA exposure on macrophage cell viability, cell apoptosis and cellular ROS level, and detected prominent cytokines release by RAW264.7. The results indicated that the cell viability of macrophage RAW264.7 was decreased by PFOA in dose- and time-dependent manners. Specifically, the exposure of 200 μM PFOA significantly increased apoptosis and ROS generation in macrophage, and thus caused cell damage. The ELISA results displayed that 100 μM PFOA exposure induced macrophage activation and enhanced cytokines secretion, including TNF-α, IL-1, IL-6, and IL-12. We also conducted nontargeted metabolomics based on LC-MS/MS and unveiled the perturbed metabolic pathways in macrophages induced by sublethal doses of PFOA (10 μM and 100 μM). Remarkably, global metabolomics results displayed that 10 μM PFOA exposure affected glutamine related pathways and the exposure at 100 μM conspicuously changed glutathione and fatty acid oxidation metabolism. These findings showed that 10 μM PFOA exposure could impel metabolic reprogramming of macrophage to trigger inflammatory response, although such dose displayed no obvious effect on cell viability, cellular ROS or apoptosis events of macrophage RAW264.7.http://www.sciencedirect.com/science/article/pii/S0147651321002396MacrophagePFOAImmunotoxicityMetabolomics |
spellingShingle | Jinglin Tian Yanjun Hong Zhenchi Li Zhiyi Yang Bo Lei Jianjun Liu Zongwei Cai Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage Ecotoxicology and Environmental Safety Macrophage PFOA Immunotoxicity Metabolomics |
title | Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage |
title_full | Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage |
title_fullStr | Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage |
title_full_unstemmed | Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage |
title_short | Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage |
title_sort | immunometabolism modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage |
topic | Macrophage PFOA Immunotoxicity Metabolomics |
url | http://www.sciencedirect.com/science/article/pii/S0147651321002396 |
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