Abstract
IL-1 functions as an essential pro-inflammatory mediator for the sensitisation of allergic contact dermatitis (ACD). However, studies conducted to date have typically used a limited number of haptens and examined their effects only on murine ACD or murine dendritic cells (DCs). It therefore remains unclear whether IL-1α and/or IL-1β is produced in ACD induced by haptens other than those commonly used in mouse ACD models, and whether they are essential for sensitisation leading to ACD in humans. In addition, it is unclear whether human DCs also produce IL-1α or IL-1β after stimulation by haptens in general. Here, we first demonstrated that 10 haptens (3 extreme, 1 strong, 3 moderate and 3 weak) increased both IL-1α mRNA and IL-1β mRNA expression by the human monocyte cell line THP-1, a commonly used surrogate of DCs in in vitro skin sensitisation tests. Next, we constructed an in vitro skin sensitisation test using a stable IL-1β reporter cell line, THP-G1b, and evaluated whether 88 haptens and 34 non-haptens increase IL-1β reporter activity. We found that 94% of 77 haptens evaluated after considering their applicability domain and solubility in the chosen media stimulated reporter activity. These studies demonstrated that most haptens, irrespective of their potency, increased IL-1β mRNA expression by THP-1 cells, confirming that human DCs also produce IL-1β after stimulation by most haptens. The luciferase assay using THP-G1b cells is thus another skin sensitisation test based on the adverse outcome pathway with reasonable performance.
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Acknowledgement
This study was supported by Grants-in-Aid from the Ministry of Economy, Trade and Industry (METI), Japan, the Ministry of Health, Labour and Welfare (MHLW), Japan, and the Japanese Society for Alternatives to Animal Experiments (JSAAE).
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This study was supported by Grants-in-Aid from the Ministry of Economy, Trade and Industry (METI), Japan, the Ministry of Health, Labour and Welfare (MHLW), Japan, and the Japanese Society for Alternatives to Animal Experiments (JSAAE), Japan.
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by HT, CF, YK and SA. The first draft of the manuscript was written by SA, and all authors commented on the manuscript. All authors read and approved the final manuscript.
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Terui, H., Kimura, Y., Fujimura, C. et al. The IL-1 promoter-driven luciferase reporter cell line THP-G1b can efficiently predict skin-sensitising chemicals. Arch Toxicol 95, 1647–1657 (2021). https://doi.org/10.1007/s00204-021-03022-2
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DOI: https://doi.org/10.1007/s00204-021-03022-2