Potential of in vitro reconstituted 3D human airway epithelia (MucilAir™) to assess respiratory sensitizers

被引:70
作者
Huang, Song [1 ]
Wiszniewski, Ludovic [1 ]
Constant, Samuel [1 ]
Roggen, Erwin [2 ]
机构
[1] Epithelix Sarl, CH-1228 Geneva, Switzerland
[2] Novozymes, DK-2880 Bagsvaerd, Denmark
关键词
Airway epithelia; Respiratory sensitization; Biomarkers; In vitro assay; MucilAir; NF-KAPPA-B; TRANSCRIPTION FACTOR; ASTHMA; ALLERGY; DISEASE; GENE; CELL; LOCALIZATION; INFLAMMATION; MECHANISMS;
D O I
10.1016/j.tiv.2012.10.010
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Respiratory sensitizers are considered as substances of higher risk, at the same level as carcinogens, mutagens and toxic chemicals for reproduction. Presently, there is no validated assay for identifying the respiratory sensitizers. Based on a fully differentiated and functional in vitro cell model of the human airway epithelium, MucilAir (TM), we attempt to develop such assay. To this end, we invented a novel method, using Dextran as carrier, for applying the water insoluble chemicals to the apical surface of the airway epithelia. Using the Dextran carrier method, we successfully tested some reference chemical compounds known to cause respiratory sensitisation in human beings, including MDI, TMA and HCPt. Interestingly, these chemical sensitizers differentially up-regulated the releases of certain cytokines and chemokines involved in allergic responses. We believe that based on MucilAir (TM) an in vitro assay could be developed for identification and characterization of the respiratory sensitizers. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1151 / 1156
页数:6
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