TY - JOUR
T1 - Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage
AU - Tian, Jinglin
AU - Hong, Yanjun
AU - Li, Zhenchi
AU - Yang, Zhiyi
AU - Lei, Bo
AU - Liu, Jianjun
AU - Cai, Zongwei
N1 - Funding Information:
The authors would like to acknowledge the financial support from National Key Research and Development Program of China ( 2017YFC1600500 ) and the National Natural Science Foundation of China ( 21707112 ).
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - Immunotoxicity
KW - Macrophage
KW - Metabolomics
KW - PFOA
UR - http://www.scopus.com/inward/record.url?scp=85103106913&partnerID=8YFLogxK
U2 - 10.1016/j.ecoenv.2021.112128
DO - 10.1016/j.ecoenv.2021.112128
M3 - Journal article
C2 - 33773150
AN - SCOPUS:85103106913
SN - 0147-6513
VL - 215
JO - Ecotoxicology and Environmental Safety
JF - Ecotoxicology and Environmental Safety
M1 - 112128
ER -
