Department of Genetics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
J Biochem Mol Toxicol. 2010 Jan-Feb;24(1):10-20. doi: 10.1002/jbt.20307.
In the epidermis, keratinocytes are involved in physical and first-line immune protection of the host. In this study, we analyzed the molecular responses to certain contact sensitizers (2,4-dinitrochlorobenzene and NiSO(4)) and irritants (sodium dodecyl sulfate and benzalkonium chloride) in cultured human keratinocytes from the bulge region of a plucked hair follicle (bulge-derived keratinocytes [BDKs]) and compared these molecular responses to those with the human monocytic leukemia cell line, THP-1. The BDKs, individually established without invasive biopsies, showed high reactivity to these stimulants. As a primary response to the contact sensitizers, the NRF2-mediated signaling pathway was upregulated in BDKs and THP-1. The expression of IL1B and IL8 genes was not induced by the irritants but by the sensitizers in THP-1. However, the expression of the IL1B and IL8 genes was induced at higher levels by the irritants in BDKs than by the sensitizers. Many genes orchestrating keratinocyte differentiation, including ID2, were significantly upregulated in response to the sensitizers in BDKs but not those in THP-1. The use of the ID2 gene to discriminate between sensitizers and irritants might be effective as a novel marker for application during in vitro sensitization with BDKs.
在表皮中，角质形成细胞参与宿主的物理和一线免疫保护。在这项研究中，我们分析了培养的来自拔毛毛囊隆起部位（隆起衍生角质形成细胞 [BDK]）的人角质形成细胞对某些接触致敏剂（2,4-二硝基氯苯和 NiSO4）和刺激物（十二烷基硫酸钠和苯扎氯铵）的分子反应，并将这些分子反应与人类单核白血病细胞系 THP-1 进行了比较。BDK 是在没有侵入性活检的情况下单独建立的，对这些刺激物表现出高反应性。作为对接触致敏剂的主要反应，BDK 和 THP-1 中的 NRF2 介导的信号通路被上调。IL1B 和 IL8 基因的表达不受刺激物诱导，但受刺激物诱导。然而，在 BDK 中，刺激物诱导的 IL1B 和 IL8 基因表达水平高于刺激物。许多协调角质形成细胞分化的基因，包括 ID2，在 BDK 中对刺激物的反应明显上调，但在 THP-1 中则没有。使用 ID2 基因来区分致敏剂和刺激物可能是有效的，因为它是一种新的标记物，可用于 BDK 的体外致敏。
