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ID 65956
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Nagahata, Taichi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Tsujino, Yoshio Graduate School of Science, Technology and Innovation, Kobe University
Takayama, Eiji Department of Oral Biochemistry, Asahi University School of Dentistry
Hikasa, Haruka Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Satoh, Ayano Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID publons researchmap
Abstract
Skin sensitization is an allergic reaction caused by certain chemical substances, and is an important factor to be taken into consideration when evaluating the safety of numerous types of products. Although animal testing has long been used to evaluate skin sensitization, the recent trend to regulate such testing has led to the development and use of alternative methods. Skin sensitization reactions are summarized in the form of an adverse outcome pathway consisting of four key events (KE), including covalent binding to skin proteins (KE1), keratinocyte activation (KE2), and dendritic cell activation (KE3). Equivalent alternative methods have been developed for KE1 to KE3, but no valid alternative has yet been developed for the evaluation of KE4 and T‑cell activation. Current alternative methods rely on data from KE1 to KE3 to predict the effect of chemicals on skin sensitization. The addition of KE4 data is expected to improve the accuracy and reproducibility of such predictions. The aim of this study was to establish an assay to evaluate KE4 T‑cell activation to supplement data on skin sensitization related to KE4. To evaluate T‑cell activation, the Jurkat T‑cell line stably expressing luciferase downstream of the pro‑inflammatory cytokine interleukin‑2 promoter was used. After exposure to known skin sensitizing agents and control substances, luciferase activity measurements revealed that this assay was valid for evaluating skin sensitization. However, two skin sensitizers known to have immunosuppressive effects on T‑cells reacted negatively in this assay. The results revealed that this assay simultaneously allows for monitoring of the skin sensitization and immuno‑suppressiveness of chemical substances and supplements KE4 T‑cell activation data, and may thus contribute to reducing the use of animal experiments.
Keywords
skin sensitization
immunotoxicity
interleukin-2 promoter
Jurkat
T-cell activation
Published Date
2021-11-08
Publication Title
Biomedical Reports
Volume
volume16
Issue
issue1
Publisher
Spandidos Publications
Start Page
3
ISSN
2049-9434
Content Type
Journal Article
language
English
OAI-PMH Set
岡山大学
Copyright Holders
© Nagahata et al.
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publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.3892/br.2021.1486
License
https://creativecommons.org/licenses/by-nc-nd/4.0/
Citation
Nagahata T, Tsujino Y, Takayama E, Hikasa H and Satoh A: Evaluation of skin sensitization based on interleukin‑2 promoter activation in Jurkat cells. Biomed Rep 16: 3, 2022
Funder Name
Japan Society for the Promotion of Science
助成番号
18K06133