NR4A orphan nuclear receptor family in peripheral blood eosinophils from patients with atopic dermatitis and apoptotic eosinophils in vitro
NR4A orphan nuclear receptor family in peripheral blood eosinophils from patients with atopic dermatitis and apoptotic eosinophils in vitro
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DOI：
10.1159/000085430
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发表时间：
2005-01-01
影响因子：
2.8
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Kagaya, S;Hashida, R;Saito, H
为了鉴定与特应性皮炎（AD）临床体征相关的新基因，研究人员在AD患者和健康志愿者的外周血嗜酸性粒细胞中寻找差异表达的基因。利用嗜酸性粒细胞制备RNA，利用Affymetrix基因芯片监测各种基因的表达，并通过实时RT-PCR定量表达。NR4A孤儿核受体家族成员Nur77和NOR1两个基因在AD患者中的表达水平明显高于健康志愿者。在AD患者中，NR4A受体家族中的另一个基因Nurr1的表达也高于健康志愿者。当分离健康志愿者外周血白细胞时，NOR1在嗜酸性粒细胞中表达最高，但Nur77和Nurr1基因的表达不是嗜酸性粒细胞特异性的。用CD30和Fas抗体（Ab）处理嗜酸性粒细胞和嗜酸性粒细胞细胞系AML14.3D10，均诱导了极强的细胞凋亡。抗cd30抗体处理能快速表达NR4A受体家族基因，而抗fas抗体处理不能。MAPK抑制剂U0126能下调NR4A孤儿核受体家族基因的表达和随后的嗜酸性粒细胞凋亡。这些结果提示，通过CD30信号通路表达NR4A受体家族基因可能调控AD等过敏性疾病中嗜酸性粒细胞凋亡。版权所有(C) 2005 S. Karger AG，巴塞尔。
To identify novel genes related to the clinical signs of atopic dermatitis (AD), differentially expressed genes were sought in peripheral blood eosinophils from both AD patients and healthy volunteers. RNA was prepared from eosinophils, expression of various genes was monitored using the Affymetrix GeneChip, and expression was quantified by real-time RT-PCR. Two genes, Nur77 and NOR1, members of NR4A orphan nuclear receptor family, were expressed at a significantly higher level in AD patients than in healthy volunteers. Expression of another gene in the NR4A receptor family, Nurr1, was also higher in AD patients than in healthy volunteers. When peripheral blood leukocytes from healthy volunteers were fractionated, NOR1 expression was highest in eosinophils, but expression of Nur77 and Nurr1 genes was not eosinophil-specific. Extremely intense apoptosis was induced in both eosinophils and an eosinophil cell line, AML14.3D10, by treatment with antibody (Ab) to both CD30 and Fas. Rapid expression of the genes for the NR4A receptor family was observed with anti-CD30 Ab treatment but not with anti-Fas Ab. The NR4A orphan nuclear receptor family gene expression and the subsequent eosinophil apoptosis were downregulated by the MAPK inhibitor, U0126. These results suggest that the expression of the NR4A receptor family genes through CD30 signaling may regulate eosinophil apoptosis in allergic conditions such as AD. Copyright (C) 2005 S. Karger AG, Basel.