Differential effects of systemic interleukin-1β on gene expression in brainstem noradrenergic nuclei.
Differential effects of systemic interleukin-1β on gene expression in brainstem noradrenergic nuclei.
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全身白介素-1β 对脑干去甲肾上腺素能核基因表达的不同影响。
DOI：
10.1016/j.lfs.2011.10.006
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发表时间：
2012
期刊：
影响因子：
6.1
通讯作者：
MohanKumar,ShebaMJ
中科院分区：
文献类型：
--
作者：
Sirivelu,MadhuP;MohanKumar,PS;MohanKumar,ShebaMJ
目的细胞因子白细胞介素-1 β（IL-1β）对神经内分泌系统有特异性的作用，如抑制生殖轴和刺激应激轴。IL-1β产生这些差异效应的机制尚不清楚。由于去甲肾上腺素（NE）参与了上述作用，我们推测IL-1β作用于脑干NE能核团，影响NE合成酶、细胞因子及相关转录因子的基因转录。对照动物接受PBS-BSA，治疗组在中午腹膜内接受5μg大鼠重组IL-1β。分别于下午1、3、5点（n=6/组）处死大鼠，用qPCR方法检测酪氨酸羟化酶（TH）mRNA的表达，或于下午3点用qPCR芯片检测TH mRNA的表达。在孤束核，5 pm时IL-1β处理后TH mRNA水平显著降低。与对照组相比，IL-1β处理组在5 pm时蓝斑TH mRNA水平显著升高。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数倍。意义IL-1β的全身给药导致脑干去甲肾上腺素能核中酪氨酸羟化酶和几种趋化因子表达的显著变化，从而介导其神经内分泌效应。
AIMSThe 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 METHODSAdult female Sprague Dawley rats in proestrus were divided into two groups. Control animals received PBS-BSA and the treatment group received 5μg of rat recombinant IL-1β i.p. at noon. They were sacrificed in groups at 1, 3 and 5pm (n=6/group) for measurement of tyrosine hydroxylase (TH) mRNA by qPCR or at 3pm for mRNA analysis by qPCR array.KEY FINDINGSTH 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 5pm. In the locus coeruleus, TH mRNA levels increased significantly at 5pm 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.SIGNIFICANCESystemic 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.