The IL-1 promoter-driven luciferase reporter cell line THP-G1b can efficiently predict skin-sensitising chemicals

Hitoshi Terui, Yutaka Kimura, Chizu Fujimura, Setsuya Aiba

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1647-1657
Number of pages11
JournalArchives of Toxicology
Volume95
Issue number5
DOIs
Publication statusPublished - 2021 May
Externally publishedYes

Keywords

  • Lipophilic chemicals
  • Luciferase assay
  • Reporter assay
  • Skin sensitisation test

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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