Reduced birth defects caused by maternal immune stimulation may involve increased expression of growth promoting genes and cytokine GM-CSF in the spleen of diabetic ICR mice
Reduced birth defects caused by maternal immune stimulation may involve increased expression of growth promoting genes and cytokine GM-CSF in the spleen of diabetic ICR mice
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DOI：
10.1016/s1567-5769(03)00200-5
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发表时间：
2003-11-01
影响因子：
5.6
通讯作者：
Holladay, SD
中科院分区：
文献类型：
--
作者：
Punareewattana, K;Sharova, LV;Holladay, SD
小鼠的母体免疫刺激可减少由各种原因引起的胎儿畸形。由激活的免疫细胞产生的生长因子被认为是可能对胎盘或胚胎发挥作用的关键介质。糖尿病会扰乱细胞因子的分泌，这可能与糖尿病胚胎病变有关。在本研究中使用了三种不同的母体免疫刺激方法：足垫注射完全弗氏佐剂(CFA)，腹腔注射(Ip)，它们对糖尿病胚胎病变的减少大致相同。注射粒细胞-巨噬细胞集落刺激因子(GM-CSF)。注射干扰素-γ(干扰素-γ)。然后使用基因微阵列来检测选定的基因组在脾白细胞中的表达。我们假设母体免疫刺激可能通过克服糖尿病小鼠免疫细胞基因表达模式的改变而起作用，这部分减轻了糖尿病的致畸效应。进一步看来，由不同的免疫刺激程序引起的脾基因表达变化的共同特征可能被识别出来，并与减少畸形发生有关。这三个过程产生了一个共同的改变的基因表达谱。显著受影响的基因包括凋亡和抗凋亡基因，以及控制细胞增殖的基因，可能反映了免疫激活的状态。GM-CSF基因被所有三种免疫刺激程序上调。该基因的蛋白产物调节胎盘发育，最近发现与乌拉坦暴露后免疫刺激的怀孕小鼠的腭裂减少有关。这些数据表明，进一步研究GM-CSF作为减少畸胎原挑战和免疫刺激小鼠出生缺陷的中介是有必要的。(C)2003爱思唯尔B.V.保留所有权利。
Maternal immune stimulation in mice decreases fetal abnormalities caused by diverse etiologies. Growth factors produced by activated immune cells were proposed to be key mediators that may exert their effects on placenta or embryo. Diabetes disrupts the secretion of cytokines, which may associate with diabetic embryopathy. Three different methods of maternal immune stimulation that result in approximately equal reduction of diabetic embryopathy were used in the present studies: footpad injection with complete Freund's adjuvant (CFA), intraperitoneal (i.p.) injection with granulocyte-macrophage colony-stimulating factor (GM-CSF), or i.p. injection with interferon-gamma (IFN-gamma). A gene microarray was then used to examine expression of a selected gene panel in splenic leukocytes. We hypothesized that maternal immune stimulation may act by overcoming altered gene expression patterns of immune cells in the diabetic mice, which partially mitigates the teratogenic effect of diabetes. It further seemed likely that a shared profile of splenic gene expression changes induced by the different immune stimulation procedures may be identified and related to reduced teratogenesis. The three procedures produced a common altered gene expression profile. Significantly affected genes included apoptotic and anti-apoptotic genes, and genes controlling cellular proliferation, and likely reflect a state of immune activation. The GM-CSF gene was up-regulated by all three immune stimulation procedures. The protein product of this gene regulates placental development, and was recently associated with reduced cleft palate in immune-stimulated pregnant mice after exposure to urethane. These data suggest that further studies of GM-CSF as mediator of reduced birth defects in teratogen-challenged, immune-stimulated mice are warranted. (C) 2003 Elsevier B.V. All rights reserved.