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Intégration des modèles in vitro dans la stratégie d'évaluation de la sensibilisation cutanée

Abstract : Abstract : Since the animal testing ban in 2013 by Cosmetics Regulation n°1223/2009, various in vitro methods have been developed. However, according to a scientific consensus, no single method can stand-alone to cover the different key events (KE) defined for skin sensitization.After a state of the art of alternative methods relating to skin sensitization, we selected and compared 3 tests to determine the best strategy to follow. In order to propose a new integrated test, we wanted to address all KE within the same cell line. Because dendritic cell (DC) plays a key role in the development of allergic contact dermatitis (ACD), we have chosen the pro-monocytic human line THP-1.We have studied as initial events (KE1), reactive oxygen species (ROS) and glutathione (GSH), Nrf2-Keap1 pathway (central detoxification pathway) and gene expression for KE2 as well as phenotypic modifications for KE3.We have shown that strong allergens are correlated with early production of FRO associated with GSH reduction. They also activate the Nrf2-Keap1 pathway and induce the expression of CD54 and CD86 cell surface markers as well as production of specific cytokines (IL-8, IL-18, etc.).To conclude, this work propose a new assay integrating all the biological measures as different KEs within the same cell.
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Submitted on : Friday, July 27, 2018 - 1:01:27 AM
Last modification on : Tuesday, October 20, 2020 - 11:04:25 AM

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Elodie Clouet. Intégration des modèles in vitro dans la stratégie d'évaluation de la sensibilisation cutanée. Toxicologie. Université Paris Saclay (COmUE), 2018. Français. ⟨NNT : 2018SACLS003⟩. ⟨tel-01850196⟩

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