The THP-1 cell toolbox: a new concept integrating the key events of skin sensitization

Archives of Toxicology
Elodie ClouetSaadia Kerdine-Römer

Abstract

According to the current scientific consensus, one in vitro test is insufficient to cover the key events (KE) defined by the adverse outcome pathway (AOP) for skin sensitization. To address this issue we combined different end points in the same cell line to cover all KEs defined by the skin sensitization AOP. Since dendritic cells (DC) play a key role in the sensitization phase leading to the development of allergic contact dermatitis (ACD), we used THP-1 cells as a surrogate for DC. We measured ROS production and GSH depletion for KE1 (binding to proteins), Nrf2 activation pathway and gene expressions for KE2 (keratinocyte response), phenotype modifications using cell-surface markers and cytokine production for KE3 (DC activation), and T-cell proliferation for KE4 (T-cell activation). These measurements were performed using the THP-1 cell line and an original THP-1/T-cell co-culture system following exposure to a variety of chemicals, including irritant, non-sensitizers, and chemicals sensitizers (pro/prehaptens). Results showed that treatment with sensitizers such as cinnamaldehyde (100 µM) or methylisothiazolinone (150 µM) was able to trigger the three main key events (KE1, KE2, and KE3) of the sensitization phase of ACD in...Continue Reading

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Methods Mentioned

BETA
FACS
flow cytometry
Profiler
ELISA
protein array
chemical stress

Software Mentioned

Prism
GraphPad
CellQuest
ImageLab
REACH

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