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Effects of benzotriazole UV stabilizers, UV-PS and UV-P, on the differentiation of splenic regulatory T cells via aryl hydrocarbon receptor

Ecotoxicology and environmental safety, 2022-06, Vol.238, p.113549-113549, Article 113549 [Peer Reviewed Journal]

2022 The Authors ;Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. ;ISSN: 0147-6513 ;EISSN: 1090-2414 ;DOI: 10.1016/j.ecoenv.2022.113549 ;PMID: 35500401

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  • Title:
    Effects of benzotriazole UV stabilizers, UV-PS and UV-P, on the differentiation of splenic regulatory T cells via aryl hydrocarbon receptor
  • Author: Kubota, Atsuhito ; Terasaki, Masaru ; Sakuragi, Yuuta ; Muromoto, Ryuta ; Ikeda-Araki, Atsuko ; Takada, Hideshige ; Kojima, Hiroyuki
  • Subjects: Aryl hydrocarbon receptor ; Benzotriazole UV stabilizer ; DR-EcoScreen cell ; Plastic additive ; Regulatory T cell ; UV-PS
  • Is Part Of: Ecotoxicology and environmental safety, 2022-06, Vol.238, p.113549-113549, Article 113549
  • Description: Benzotriazole UV stabilizers (BUVSs) are widely used as additives in various materials, including plastics, to prevent damage from UV-irradiation. However, despite the extensive usage of BUVSs, information on their toxicological properties is limited. In this study, we investigated the effect of BUVSs on the immune regulatory system via the aryl hydrocarbon receptor (AhR). A cell-based transactivation assay using DR-EcoScreen cells revealed that, among 13 BUVSs tested, UV-P, UV-PS, UV-9, and UV-090 activated AhR in a dose-dependent manner. In particular, the AhR agonistic activity of UV-PS was about 10-fold more potent than those of UV-P, UV-090, and UV-9, and UV-PS acted as a full agonist against AhR. In order to investigate the immune regulatory effects of these BUVSs, we orally treated C57BL/6 mice with UV-PS or UV-P (10, 30, and 100 mg/kg) and studied the differentiation of regulatory T cells (Tregs) in spleen cells. Flow-cytometry analysis revealed that the administration of UV-PS (30 and 100 mg/kg) or UV-P (100 mg/kg) significantly increased the population of CD4+-/CD25+-/Foxp3+ Tregs in the spleen. In addition, we found that the in vitro exposure of mouse splenocytes to UV-PS (10 and 30 μM) or UV-P (30 μM) as well as to TCDD (0.1 nM) significantly induced Tregs. Notably, the induction of Tregs was eliminated by co-treatment with an AhR antagonist, CH-223191, in each case. Taken together, these findings suggest that some BUVSs might induce Tregs through direct AhR activation and act as immunosuppressive modulators. [Display omitted] •UV-P, UV-PS, UV-9, and UV-090 activated AhR.•UV-PS showed 10-fold more potent AhR activity than did UV-P, UV-9, and UV-090.•Oral treatment of mice with UV-PS or UV-P significantly induced splenic Treg.•In vitro treatment of mouse splenocytes with UV-PS or UV-P significantly induced Treg.•Treg induction by UV-PS or UV-P was eliminated by co-treatment with an AhR antagonist.
  • Publisher: Netherlands: Elsevier Inc
  • Language: English
  • Identifier: ISSN: 0147-6513
    EISSN: 1090-2414
    DOI: 10.1016/j.ecoenv.2022.113549
    PMID: 35500401
  • Source: Open Access: DOAJ Directory of Open Access Journals
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