Oxidation of Cell Surface Thiol Groups by Contact Sensitizers Triggers the Maturation of Dendritic Cells
Oxidation of Cell Surface Thiol Groups by Contact Sensitizers Triggers the Maturation of Dendritic Cells
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DOI：
10.1038/jid.2009.229
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发表时间：
2010-01-01
影响因子：
6.5
通讯作者：
Aiba, Setsuya
中科院分区：
文献类型：
--
作者：
Kagatani, Saori;Sasaki, Yoshinori;Aiba, Setsuya
p38丝裂原活化蛋白激酶（MAPK）在致敏剂诱导树突状细胞（DC）成熟过程中起重要作用。最近，有报道说，细胞表面硫醇的氧化由外源性不渗透硫醇氧化剂可以磷酸化p38 MAPK。在这项研究中，我们研究了敏化剂是否氧化单核细胞衍生的DC（MoDC）的细胞表面硫醇。当使用Alexa fluor马来酰亚胺通过流式细胞术定量细胞表面硫醇时，我们检查的所有敏化剂都减少了MoDC上的细胞表面硫醇。为了研究敏化剂对DC成熟的细胞表面硫醇减少的影响，我们分析了不渗透的硫醇氧化剂邻菲咯啉铜络合物（CuPhen）的影响。用CuPhen处理MoDC减少了细胞表面巯基，磷酸化p38 MAPK，并诱导MoDC成熟，即CD 83，CD 86，HLA-DR和IL-8 mRNA的增加，以及水通道蛋白-3 mRNA的下调。当用N-乙酰-L-半胱氨酸预处理或用SB 203580处理时，CD 86的增加被显著抑制。最后，我们表明，在小鼠皮肤上的表皮应用2，4-二硝基氯苯显着降低体内朗格汉斯细胞的细胞表面硫醇。这些数据表明，细胞表面硫醇的氧化在敏化剂引发DC成熟中具有一定作用。
p38 mitogen-activated protein kinase (MAPK) has a crucial role in the maturation of dendritic cells (DCs) by sensitizers. Recently, it has been reported that the oxidation of cell surface thiols by an exogenous impermeant thiol oxidizer can phosphorylate p38 MAPK. In this study, we examined whether sensitizers oxidize cell surface thiols of monocyte-derived DCs (MoDCs). When cell surface thiols were quantified by flow cytometry using Alexa fluor maleimide, all the sensitizers that we examined decreased cell surface thiols on MoDCs. To examine the effects of decreased cell surface thiols by sensitizers on DC maturation, we analyzed the effects of an impermeant thiol oxidizer, o-phenanthroline copper complex (CuPhen). The treatment of MoDCs with CuPhen decreased cell surface thiols, phosphorylated p38 MAPK, and induced MoDC maturation, that is, the augmentation of CD83, CD86, HLA-DR, and IL-8 mRNA, as well as the downregulation of aquaporin-3 mRNA. The augmentation of CD86 was significantly suppressed when MoDCs were pretreated with N-acetyl-L-cystein or treated with SB203580. Finally, we showed that epicutaneous application of 2,4-dinitrochlorobenzene on mouse skin significantly decreased cell surface thiols of Langerhans cells in vivo. These data suggest that the oxidation of cell surface thiols has some role in triggering DC maturation by sensitizers.