Miyazawa Masaaki, Ito Yuichi, Yoshida Yukiko, Sakaguchi Hitoshi, Suzuki Hiroyuki
Safety and Microbial Control Research Center, Kao Corporation, 2606 Akabane, Ichikai-Maich, Haga-Gun Tochigi 321-3497, Japan.
Toxicol In Vitro. 2007 Apr;21(3):428-37. doi: 10.1016/j.tiv.2006.10.005. Epub 2006 Oct 14.
In the induction phase of allergic contact hypersensitivity, dendritic cells (DCs), including Langerhans cells (LCs) present in epidermis, can trigger an efficient T cell response once they have matured in response to an allergen. Upon maturation, DCs have been shown to induce expression of several surface molecules and the up-regulation of cytokine production. We have previously shown that THP-1 cells, human acute monocytic leukemia cell line, can discriminate between allergens and irritants by measuring expression of surface markers, CD86 and CD54, following chemical exposure. At the same time, we have also reported that augmented expression of HLA and CD80, and production of IL-1beta were up-regulated in THP-1 cells when treated with an allergen, 2,4-dinitrochlorobenzene (DNCB). In the present study, we first evaluated whether THP-1 cells induced the phenotypic changes and the production of cytokines, which are observed in the process of DC maturation, when treated with two known allergens, DNCB and nickel sulfate (NiSO(4)), and one irritant (sodium lauryl sulfate (SLS)). Exposure to DNCB and NiSO(4) induced significant augmentation of CD40 and CD83 expression as well as CD86 and CD54. Also, TNF-alpha and IL-8 secretion were markedly induced by DNCB and NiSO(4) in a dose-dependent manner. In addition, DNCB and NiSO(4) augmented CD1a expression and production of IL-6, respectively. On the contrary, SLS did not change any of these markers. We then evaluated a series of chemicals, including six known allergens (e.g., hydroquinone (HQ)) and two non-allergens (e.g., methyl paraben (MP)), in order to investigate the potential increase of CD86, CD54, CD40, and CD83 expression on THP-1 cells, and production of TNF-alpha and IL-8. Indeed, all tested allergens, except eugenol (EU), caused significant increased changes in at least four of the analyzed six markers, while non-allergens did not induce any changes. EU significantly augmented CD86, CD54 and CD40 expression. These results revealed that the wide variety of responses to allergens in THP-1 cells may emulate allergen-induced maturation processes of DCs. It is suggested that THP-1 cells, which could develop several DC-like properties, are suitable for identifying sensitizing potential of chemicals.
在过敏性接触超敏反应的诱导阶段,树突状细胞(DCs),包括表皮中的朗格汉斯细胞(LCs),一旦在接触过敏原后成熟,就能触发有效的T细胞反应。成熟后,DCs已被证明可诱导多种表面分子的表达并上调细胞因子的产生。我们之前已经表明,人急性单核细胞白血病细胞系THP-1细胞可以通过测量化学物质暴露后表面标志物CD86和CD54的表达来区分过敏原和刺激物。同时,我们还报道,用过敏原2,4-二硝基氯苯(DNCB)处理THP-1细胞时,HLA和CD80的表达增加以及IL-1β的产生上调。在本研究中,我们首先评估了用两种已知过敏原DNCB和硫酸镍(NiSO₄)以及一种刺激物(十二烷基硫酸钠(SLS))处理THP-1细胞时,是否会诱导DC成熟过程中观察到的表型变化和细胞因子的产生。接触DNCB和NiSO₄会显著增加CD40和CD83的表达以及CD86和CD54的表达。此外,DNCB和NiSO₄以剂量依赖的方式显著诱导TNF-α和IL-8的分泌。此外,DNCB和NiSO₄分别增加了CD1a的表达和IL-6的产生。相反,SLS没有改变这些标志物中的任何一个。然后,我们评估了一系列化学物质,包括六种已知过敏原(如对苯二酚(HQ))和两种非过敏原(如对羟基苯甲酸甲酯(MP)),以研究THP-1细胞上CD86、CD54、CD40和CD83表达以及TNF-α和IL-8产生的潜在增加。事实上,除丁香酚(EU)外,所有测试的过敏原至少在分析的六个标志物中的四个上引起了显著的增加变化,而非过敏原没有诱导任何变化。EU显著增加了CD86、CD54和CD40的表达。这些结果表明,THP-1细胞对过敏原的多种反应可能模拟了DC的过敏原诱导成熟过程。有人提出,能够发展出几种类似DC特性的THP-1细胞适合用于鉴定化学物质的致敏潜力。