Lourenço A C S, Galbiati V, Corti D, Papale A, Martino-Andrade A J, Corsini E
Department of Pharmacology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Toxicol In Vitro. 2015 Dec;29(8):2001-8. doi: 10.1016/j.tiv.2015.08.011. Epub 2015 Aug 28.
Recent studies suggest that phthalates may have a role in the development of allergic diseases, probably due to an adjuvant effect. The present study aimed to investigate the possible adjuvant effect of dibutyl phthalate (DBP) in two in vitro models of contact-allergen induced cell activation, namely the NCTC 2544 IL-18 assay and the THP-1 activation assay. Results show no adjuvant effect in the human keratinocyte cell line NCTC 2544, indicated by lack of increase in interleukin 18 (IL-18) production after exposure to p-Phenylenediamine (PPD) in association with DBP. On the contrary, increased upregulation of CD86 and interleukin 8 (IL-8) production were observed in THP-1 cells exposed to combinations of citral (Cit) or imidazolidinyl urea (IMZ) with DBP, indicative of an adjuvant effect. Additionally, higher production of reactive oxygen species (ROS) in THP-1 cells treated with DBP associated to Cit supports that oxidative stress could be part of the molecular mechanism of the observed adjuvant effect. In conclusion, we demonstrate that DBP presents in vitro an adjuvant effect for immune stimulation in dendritic cells but not in keratinocytes. Future studies are necessary to elucidate the precise mechanism underlying the adjuvant effect of DBP in vitro and in vivo.
最近的研究表明，邻苯二甲酸盐可能在过敏性疾病的发展中起作用，这可能归因于其佐剂效应。本研究旨在探讨邻苯二甲酸二丁酯（DBP）在两种接触性过敏原诱导的细胞活化体外模型中的可能佐剂效应，即NCTC 2544 IL-18检测法和THP-1活化检测法。结果显示，在人角质形成细胞系NCTC 2544中未观察到佐剂效应，这表现为在与DBP联合接触对苯二胺（PPD）后，白细胞介素18（IL-18）的产生没有增加。相反，在暴露于柠檬醛（Cit）或咪唑烷基脲（IMZ）与DBP组合的THP-1细胞中，观察到CD86上调增加和白细胞介素8（IL-8）产生增加，这表明存在佐剂效应。此外，在用与Cit相关的DBP处理的THP-1细胞中，活性氧（ROS）的产生更高，这支持氧化应激可能是观察到的佐剂效应分子机制的一部分。总之，我们证明DBP在体外对树突状细胞具有免疫刺激佐剂效应，但对角质形成细胞没有。未来有必要开展研究以阐明DBP体外和体内佐剂效应的精确机制。
