Central nervous system cytokine gene expression: modulation by lead.

Central nervous system cytokine gene expression: modulation by lead.
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DOI:
10.1002/jbt.20358
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发表时间:
2011-01
影响因子:
3.6
通讯作者:
Lawrence, David A.
Lawrence, David A.
中科院分区:
医学4区
文献类型:
--
作者:
Kasten-Jolly, Jane;Heo, Yong;Lawrence, David A.

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环境中的重金属毒物铅(Pb)对儿童的中枢神经系统(CNS)的危害性大于成人,因为铅暴露会影响发育过程中的神经系统。由于生长因子和细胞因子在中枢神经系统的发展中起着非常重要的作用,我们研究了铅暴露对中枢神经系统发育过程中细胞因子表达的影响。通过微阵列、实时RT-PCR、Luminex和ELISA方法研究了出生后21天(pnd 21)小鼠的细胞因子表达。BALB/c小鼠幼崽暴露于铅通过母鼠的饮用水(0.1 mM醋酸铅),从妊娠第8天(gd 8)至pnd 21。两种细胞因子,白细胞介素-6(IL-6)和转化生长因子-β1(TGF-β1),在铅的存在下,表现出显着的变化的转录水平。IL-6和TGF-β1都具有信号转导级联,可以协同打开星形胶质细胞标志物胶质细胞酸性蛋白(GFAP)的基因。基因芯片结果表明,铅暴露显着增加GFAP的表达。铅还调节IL-6、TGF-β1和IL-18蛋白在选定脑区的表达。铅对学习和长期记忆的有害影响被认为是由于过度的星形胶质细胞生长和/或激活伴随着神经连接的干扰。脑区细胞因子的差异神经表达需要进一步研究,以机械关联铅和神经炎症与行为和认知变化。
The environmental heavy metal toxicant, lead (Pb), has been shown to be more harmful to the central nervous system (CNS) of children than to adults, given that Pb exposure affects the neural system during development. Because growth factors and cytokines play very important roles in development of the CNS, we have examined the impact of Pb exposure on the expression of cytokines during CNS development. Cytokine expression was studied in post-natal-day 21(pnd21) mice by microarray, real-time RT-PCR, Luminex, and ELISA methodologies. BALB/c mouse pups were exposed to Pb through the dam’s drinking water (0.1 mM Pb acetate), from gestation-day 8 (gd8) to pnd21. Two cytokines, interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1), displayed significantly changed transcript levels in the presence of Pb. IL-6 and TGF-β1 both have signal transduction cascades that can cooperatively turn on the gene for the astrocyte marker glial-fibrillary acidic protein (GFAP). Microarray results indicated that Pb exposure significantly increased expression of GFAP. Pb also modulated IL-6, TGF-β1, and IL-18 protein expression in select brain regions. The deleterious effects of Pb on learning and long-term memory are posited to result from excessive astrocyte growth and/or activation with concomitant interference with neural connections. Differential neural expression of cytokines in brain regions needs to be further investigated to mechanistically associate Pb and neuroinflammation with behavioral and cognitive changes.
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发表时间: 2002-03-01
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影响因子: 2.9
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