Glucocorticoid receptor BclI polymorphism associates with immunomodulatory response to stress hormone in human peripheral blood mononuclear cells.
Glucocorticoid receptor BclI polymorphism associates with immunomodulatory response to stress hormone in human peripheral blood mononuclear cells.
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DOI：
10.1111/iji.12018
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发表时间：
2013-06
影响因子：
2.2
通讯作者：
Marshall GD Jr
中科院分区：
文献类型：
--
作者：
Xiang L;Marshall GD Jr
糖皮质激素受体（GR）变异体已被发现与应激相关的疾病。我们先前的体内研究发现，GR BclI单核苷酸多态性（SNP）的CC等位基因在高应激组中更常见，高应激组的调节性T细胞（Treg）和Th 1细胞因子水平均较低。本研究旨在探讨GR Bcl I基因多态性与人外周血单个核细胞（PBMC）对应激激素的免疫调节反应的关系。收集18名正常志愿者的血液样本，其中9名为BclI多态性GG等位基因，9名为野生型（WT）CC等位基因。将PBMC与10 - 8 M地塞米松（DEX）一起培养，地塞米松模拟在心理应激24小时和11天期间观察到的血浆皮质醇水平。实时荧光定量RT-PCR分析转录因子、应激激素和细胞因子受体的基因表达。FoxP 3 mRNA在BclI WT中显著改变（在24小时降低，在11天增加），但在GG等位基因中没有改变。CC等位基因GR mRNA在24 h时表达上调，11 d时表达下调（p分别<0.01和0.05），而GG等位基因则无明显变化。β 2肾上腺素能受体（β 2 AR）在CC和GG两个等位基因中的表达在24 h时均显著增加（p<0.01和p<0.001），而在11 d时仅GG等位基因表达显著降低。DEX作用24 h后，T-bet和加塔-3的表达同时改变。GR的Bcl I多态性识别不同的免疫调节反应，皮质类固醇激素，这可能解释，至少部分地，个体敏感性的变化，压力。
Glucocorticoid receptor (GR) variants have been found to be associated with stress-related disorders. Our previous in vivo study revealed that the CC allele of GR BclI single nucleotide polymorphism (SNP) was more common in the high stress group which had lower levels of both regulatory T cells (Treg) and Th1 cytokine. The current study was to investigate associations between GR BclI polymorphism and immunomodulatory response to stress hormone in vitro in human peripheral blood mononuclear cells (PBMC). Blood samples were collected from 18 normal volunteers including 9 subjects with BclI polymorphism GG allele and 9 with wild-type (WT) CC allele. PBMC were cultured with 10−8 M dexamethasone (DEX) which mimics the plasma cortisol level observed during periods of psychological stress for 24h and 11 days. Gene expressions of transcription factors, stress hormone and cytokine receptors were analyzed by real-time RT-PCR. FoxP3 mRNA was significantly altered in the BclI WT (decreased at 24h and increased at 11-day) but not in the GG allele. GR mRNA was up-regulated at 24h and down-regulated at 11-day in CC alleles (p<0.01 and 0.05, respectively), rather than in GG alleles. The expression of β-2 adrenergic receptor (β2AR) was increased at 24h in both CC and GG alleles (p<0.01 and p<0.001), but decreased significantly at 11 days in only GG alleles. Expression of T-bet and GATA-3 was altered simultaneously in 24h culture with DEX from both groups. The BclI polymorphism of GR identifies different immunomodulatory responses to corticosteroids which may explain, at least in part, the variability in individual sensitivity to stressors.
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影响因子：
4.1
作者：
HOLSBOER, F;LAUER, CJ;KRIEG, JC
通讯作者：
KRIEG, JC
影响因子：
15.1
作者：
Kunz-Ebrecht, SR;Mohamed-Ali, V;Steptoe, A
通讯作者：
Steptoe, A
影响因子：
3.2
作者：
KIRSCHBAUM, C;PIRKE, KM;HELLHAMMER, DH
通讯作者：
HELLHAMMER, DH
影响因子：
15.1
作者：
Marshall, GD;Agarwal, SK;Morris, GJ
通讯作者：
Morris, GJ
DOI：
10.1111/j.1749-6632.2002.tb04229.x
发表时间：
2002-01-01
期刊：
NEUROENDOCRINE IMMUNE BASIS OF THE RHEUMATIC DISEASES II, PROCEEDINGS
影响因子：
--
作者：
Elenkov, IJ;Chrousos, GP
通讯作者：
Chrousos, GP