Constitutive and LPS-regulated expression of interleukin-18 receptor beta variants in the mouse brain.
Constitutive and LPS-regulated expression of interleukin-18 receptor beta variants in the mouse brain.
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DOI：
10.1016/j.bbi.2010.11.011
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Tascedda F
中科院分区：
文献类型：
--
作者：
Alboni S;Montanari C;Benatti C;Blom JM;Simone ML;Brunello N;Caggia F;Guidotti G;Marcondes MC;Sanchez-Alavez M;Conti B;Tascedda F
白细胞介素（IL）-18是一种促炎细胞因子，被认为参与成人大脑的生理和病理状况。IL-18通过异二聚体受体发挥作用，该受体由结合所需的α亚基（IL-18 R α）和激活信号转导所需的β亚基（IL-18 R β）组成。我们最近证明，典型的α结合链，其推定的诱饵亚型，在小鼠中枢神经系统（CNS）中表达，表明IL-18可以通过直接结合其受体作用于大脑。考虑到β链的共表达似乎是产生功能性受体所必需的，并且已经在大鼠和人脑中描述了该链的短变体，在本研究中，我们将研究扩展到小鼠中的IL-18 R β。使用多种方法，我们发现：1）IL-18 R β的短剪接变体在CNS中表达，即使与全长IL-18 R β变体相比水平较低2）典型IL-18 R β在CNS中表达，特别是在属于边缘系统的区域和核中，如先前对IL-18 R α观察到的，最后，我们还证实了在单次注射脂多糖（LPS）后3小时，两种IL-18 R β亚型在不同的脑区域中上调，提示CNS中的IL-18 R β可能参与介导LPS的内分泌和行为效应。我们的数据突出了小鼠大脑中IL-18调节活性的相当复杂性，并进一步支持IL-18的重要核心作用。
Interleukin (IL)-18 is a pro-inflammatory cytokine that is proposed to be involved in physiological as well as pathological conditions in the adult brain. IL-18 acts through a heterodimer receptor comprised of a subunit alpha (IL-18Rα) required for binding, and a subunit beta (IL-18Rβ) necessary for activation of signal transduction. We recently demonstrated that the canonical alpha binding chain, and its putative decoy isoform, are expressed in the mouse central nervous system (CNS) suggesting that IL-18 may act on the brain by directly binding its receptor. Considering that the co-expression of the beta chain seems to be required to generate a functional receptor and, a short variant of this chain has been described in rat and human brain, in this study we have extended our investigation to IL-18Rβ in mouse. Using a multi-methodological approach we found that: 1) a short splice variant of IL-18Rβ was expressed in the CNS even if at lower levels compared to the full-length IL-18Rβ variants 2) the canonical IL-18Rβ is expressed in the CNS particularly in areas and nuclei belonging to the limbic system as previously observed for IL-18Rα, finally 3) we have also demonstrated that both IL-18Rβ isoforms are up-regulated in different brain areas three hours after a single lipopolysaccharide (LPS) injection suggesting that IL-18Rβ in the CNS might be involved in mediating the endocrine and behavioral effects of LPS. Our data highlight the considerable complexity of the IL-18 regulation activity in the mouse brain and further support an important central role for IL-18.
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影响因子：
30.5
作者：
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