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Differential effects of systemic interleukin-1β on gene expression in brainstem noradrenergic nuclei

机译:全身性白介素-1β对脑干去甲肾上腺素能核基因表达的影响

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Aims: The cytokine, interleukin-1β (IL-1β), is known to produce specific effects on the neuroendocrine system such as suppression of the reproductive axis and stimulation of the stress axis. The mechanism by which IL-1β produces these differential effects is not clear. Since norepinephrine (NE) is involved in these effects, we hypothesized that IL-1β acts on brainstem noradrenergic nuclei to affect gene transcription of NE synthesizing enzymes, cytokines and associated transcription factors. Main methods: Adult female Sprague Dawley rats in proestrus were divided into two groups. Control animals received PBS-BSA and the treatment group received 5 μg of rat recombinant IL-1β i.p. at noon. They were sacrificed in groups at 1, 3 and 5 pm (n = 6/group) for measurement of tyrosine hydroxylase (TH) mRNA by qPCR or at 3 pm for mRNA analysis by qPCR array. Key findings: TH mRNA levels decreased gradually with time in both control and IL-1β-treated rats in the ventrolateral medulla. In the nucleus of solitary tract, TH mRNA levels were significantly reduced by IL-1β treatment at 5 pm. In the locus coeruleus, TH mRNA levels increased significantly at 5 pm with IL-1β treatment compared to controls. In the second set of animals analyzed by qPCR array, there were several fold increases in the expression of certain cytokines, chemokines, and transcription factors in specific noradrenergic nuclei. Significance: Systemic administration of IL-1β causes significant changes in the expression of tyrosine hydroxylase and several chemokines in brain stem noradrenergic nuclei, thereby mediating its neuroendocrine effects.
机译:目的:已知细胞因子白介素-1β(IL-1β)对神经内分泌系统产生特定作用,例如抑制生殖轴和刺激压力轴。 IL-1β产生这些差异作用的机制尚不清楚。由于去甲肾上腺素(NE)参与这些作用,我们假设IL-1β作用于脑干去甲肾上腺素能核以影响NE合成酶,细胞因子和相关转录因子的基因转录。主要方法:将成年雌性成年雌性Sprague Dawley大鼠分为两组。对照动物接受PBS-BSA,治疗组接受5μg大鼠重组IL-1β腹膜内注射。中午。将其在第1、3和5 pm组(n = 6 /组)处死以通过qPCR测量酪氨酸羟化酶(TH)mRNA或在3 pm通过qPCR阵列进行mRNA分析。关键发现:在腹侧延髓的对照组和经IL-1β治疗的大鼠中,TH mRNA水平均随时间逐渐降低。在孤立道细胞核中,下午1点通过IL-1β处理,TH mRNA水平显着降低。在蓝斑中,与对照组相比,IL-1β治疗在下午5点时TH mRNA水平显着增加。在通过qPCR阵列分析的第二组动物中,特定的去甲肾上腺素能核中某些细胞因子,趋化因子和转录因子的表达增加了几倍。意义:IL-1β的全身给药引起脑干去甲肾上腺素能核中酪氨酸羟化酶和几种趋化因子的表达发生显着变化,从而介导其神经内分泌作用。

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