Vitamin A status significantly alters nuclear factor-κB activity assessed by in vivo imaging

Vitamin A status significantly alters nuclear factor-κB activity assessed by in vivo imaging
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DOI:
10.1096/fj.03-1098fje
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发表时间:
2004-06-01
期刊:
影响因子:
4.8
通讯作者:
Blomhoff, R
Blomhoff, R
中科院分区:
生物学2区
文献类型:
--
作者:
Austenaa, LMI;Carlsen, H;Blomhoff, R

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我们的研究旨在研究体内维生素A状态与NF-κ B活性之间的关系,NF-κ B是一种调节炎症和免疫反应的转录因子。我们使用了一种新的转基因小鼠NF-κ B-荧光素酶报告基因模型,该模型能够通过增强的图像捕获装置对活小鼠中的NF-κ B活性进行分子成像。与对照小鼠相比,维生素A缺乏(VAD)小鼠的全身发光(反映总体NF-κ B活性)升高了2.2倍。具体而言,VAD小鼠的淋巴结和胸腺中的NF-κ B活性分别增加了1.8倍和1.4倍,与对照小鼠相比,VAD小鼠暴露于UVB辐射的皮肤中的NF-κ B诱导也增强了。VAD小鼠给予全反式维甲酸导致NF-κ B活性短暂降低,相反,给予对照小鼠单剂量RAR泛拮抗剂AGN 194310导致全身发光的显著短暂诱导。我们的研究结果表明,维生素A的状态,维生素A本身,影响NF-κ B的活性在体内,并在VAD的NF-κ B活性升高可能是一种机制的VAD综合征的一些功能。
Our study aimed to investigate, in vivo, the relationship between vitamin A status and NF-kappaB activity, a transcription factor central in regulating inflammatory and immune responses. We used a novel transgenic murine NF-kappaB-luciferase reporter model that enabled molecular imaging of NF-kappaB activity in live mice via an intensified image-capture apparatus. Whole-body luminescence, which reflects overall NF-kappaB activity, was elevated 2.2-fold in vitamin A-deficient (VAD) mice compared with control mice. Specifically, NF-kappaB activity in VAD mice was increased 1.8-fold in the lymph nodes and 1.4-fold in the thymus and, NF-kappaB induction in UVB radiation-exposed skin was also enhanced in VAD mice compared with control mice. The administration of all-trans retinoic acid to VAD mice resulted in a transient reduction in NF-kappaB activity and, conversely, a single dose of the RAR-pan-antagonist, AGN 194310, administered to control mice, led to a marked, transient induction of whole-body luminescence. Our results suggest that vitamin A status, and vitamin A itself, affects NF-kappaB activity in vivo and that the elevated NF-kappaB activity in VAD may be a mechanism underlying some of the features of VAD syndrome.