Chlorinated Polycyclic Aromatic Hydrocarbons Induce Immunosuppression in THP-1 Macrophages Characterized by Disrupted Amino Acid Metabolism
- 25 October 2022
- journal article
- research article
- Published by American Chemical Society (ACS) in Environmental Science & Technology
- Vol. 56 (22), 16012-16023
- https://doi.org/10.1021/acs.est.2c06471
Abstract
Frequent chlorinated polycyclic aromatic hydrocarbon (Cl-PAH) occurrence in environmental samples and emerging detection in human serum have warned of their underestimated risks. Studies showed that some Cl-PAHs exhibit dioxin-like properties, implying immunotoxic potential but lacking direct evidence and specific mechanisms. Here, we integrated a high-content screening (HCS) system and high-resolution mass spectrometry to investigate the immune dysfunction and metabolic disruption induced by Cl-PAHs and their parent PAHs (PPAHs) in THP-1 macrophages. Both 9-chloroanthracene and 2,7dichlorofluorene exerted clear immunosuppression on THP-1 m phi s, while their PPAHs exhibited different immune disturbances. Interestingly, Cl-PAH/PPAHs induced complex alterations in the multicytokine/chemokine network, including biphasic alterations with initial inhibition and later enhancement. Furthermore, the protein-protein interaction results revealed that inflammatory cytokines are the core of this complicated network regulation. Connecting immune phenotypes and metabolomics, amino acid metabolism reprogramming was identified as a potential cause of Cl-PAH/PAH-induced immunotoxicity. Phytosphingosine and L-kynurenine were proposed as candidate immunosuppression biomarkers upon Cl-PAH exposure. This article provides direct immunotoxicity evidence of Cl-PAHs without activating AhR for the first time and discusses the contribution of metabolites to Cl-PAH/PPAH-induced immune responses in macrophages, highlighting the potential of developing new methods based on immunometabolism mechanisms for toxic risk evaluation of environmental chemicals.Funding Information
- National Natural Science Foundation of China (No.22127810)
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