Audry Adrien, Mathiot Julianne, Muller Samuel, Coiscaud Amélie, Langonné Isabelle, Battais Fabrice, Leininger Brigitte, Sponne Isabelle
Department of Toxicology and Biometrology, National Institute for Research and Safety (INRS), rue du Morvan - 54500 Vandœuvre-lès-Nancy, France.
University of Lorraine, INSERM, UMR-1256, 9 Avenue de la Forêt de Haye - 54500 Vandœuvre-lès-Nancy, France.
Toxicol Res (Camb). 2021 Nov 26;10(6):1223-1227. doi: 10.1093/toxres/tfab101. eCollection 2021 Dec.
The mechanisms underlying chemical respiratory sensitization are incompletely understood. One of the major cell types involved in this pathology are dendritic cells. In this study, the mechanisms of the NRF2-Keap1 pathway were studied using a bone marrow-derived dendritic cell model exposed to two respiratory sensitizers: ammonium hexachloroplatinate (HCP) and ammonium tetrachloroplatinate (ATCP). Expression levels for two Nrf2-regulated genes, and , were analyzed by real time-quantitative polymerase chain reaction. A flow cytometry-based method was also developed to measure intracellular Nrf2 accumulation in dendritic cells following exposure. Exposure to HCP and ATCP increased both and gene expression, and was associated with accumulation of Nrf2 protein in cells. Overall, these results show that the respiratory sensitizers, in addition to skin sensitizers, can also induced markers associated with NRF2-Keap1 pathway activation in dendritic cells. This study contributes to a better understanding of the adverse outcome of respiratory sensitization.
化学性呼吸道致敏的潜在机制尚未完全明确。参与这种病理过程的主要细胞类型之一是树突状细胞。在本研究中，利用暴露于两种呼吸道致敏剂——六氯铂酸铵（HCP）和四氯铂酸铵（ATCP）的骨髓源性树突状细胞模型，研究了NRF2-Keap1信号通路的机制。通过实时定量聚合酶链反应分析了两个Nrf2调控基因的表达水平。还开发了一种基于流式细胞术的方法来测量暴露后树突状细胞内Nrf2的积累情况。暴露于HCP和ATCP均增加了基因表达，且与细胞内Nrf2蛋白的积累有关。总体而言，这些结果表明，除皮肤致敏剂外，呼吸道致敏剂也可诱导树突状细胞中与NRF2-Keap1信号通路激活相关的标志物。本研究有助于更好地理解呼吸道致敏的不良后果。
