IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure.
IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure.
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IL-33 通过抑制复发性新生儿癫痫大鼠模型中的细胞凋亡、自噬和 NF-κB 介导的炎症途径提供神经保护
DOI：
10.3389/fnmol.2017.00423
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发表时间：
2017
影响因子：
4.8
通讯作者：
Tao LY
中科院分区：
文献类型：
--
作者：
Gao Y;Luo CL;Li LL;Ye GH;Gao C;Wang HC;Huang WW;Wang T;Wang ZF;Ni H;Chen XP;Tao LY
白细胞介素-33 （IL-33）是IL-1家族细胞因子中新发现的与染色质相关的细胞因子。它通过由ST2L和IL-1RAcp组成的异源二聚体发出信号，在许多疾病中起着至关重要的作用。然而，对于IL-33在新生儿复发性癫痫发作（RNS）中的作用和潜在的复杂机制知之甚少。为了确定IL-33是否具有重要的调控作用，本研究建立了新生儿癫痫发作模型。大鼠吸入挥发性氟醚引起反复发作。术前分别腹腔注射重组IL-33或PBS。在这里，我们目前的结果表明，RNS有助于显著降低IL-33及其特异性受体（ST2L）在皮质中的表达。与Sham组相比，RNS诱导海马IL-33和ST2L明显升高。而注射IL-33后，大鼠脑皮质和海马区IL-33总水平均显著升高。此外，IL-33主要共定位于GFAP+星形胶质细胞的细胞核以及Iba-1+小胶质细胞和IL-33+/NeuN+融合细胞的细胞质中。ST2L主要表达于GFAP+星形胶质细胞膜、Iba-1+小胶质细胞膜和NeuN+神经元膜。此外，给予IL-33可改善rns诱导的行为缺陷，促进体重增加，并改善空间学习和记忆能力。IL-33预处理可阻断NF-κB的活化，抑制炎症因子IL-1β和TNF-α的升高，抑制RNS后细胞凋亡和自噬激活。总的来说，IL-33通过抑制RNS后NF-κ b介导的炎症途径的凋亡、自噬和至少部分抑制NF-κ b介导的炎症途径提供潜在的神经保护。
Interleukin-33 (IL-33) is a novel identified chromatin-associated cytokine of IL-1 family cytokines. It signals through a heterodimer comprised of ST2L and IL-1RAcp, and plays a crucial role in many diseases. However, very little is known about the role and underlying intricate mechanisms of IL-33 in recurrent neonatal seizure (RNS). To determine whether IL-33 plays an important regulatory role, we established a neonatal seizure model in this study. Rats were subjected to recurrent seizures induced by inhaling volatile flurothyl. Recombinant IL-33 or PBS were also administered by intraperitoneally (IP) before surgery, respectively. Here, our current results indicated that RNS contributed to a significant reduction in IL-33 and its specific receptor (ST2L) expressions in cortex. While, in hippocampus, RNS induced an increase in IL-33 and ST2L evidently, compared with Sham group. After injection with IL-33, however, a remarkable increase in total IL-33 was detected both in brain cortex and hippocampus. In addition, IL-33 was mainly co-localized in the nuclear of GFAP+ astrocytes and the cytoplasm of the Iba-1+ microglia and IL-33+/NeuN+ merged cells. In parallel, ST2L was expressed mainly in the membrane of GFAP+ astrocytes, Iba-1+ microglia and NeuN+ neurons, respectively. Furthermore, administration of IL-33 improved RNS-induced behavioral deficits, promoted bodyweight gain, and ameliorated spatial learning and memory ability. Moreover, IL-33 pretreatment blocked the activation of NF-κB, resisted inflammatory cytokines IL-1β and TNF-α increase, as well as suppressed apoptosis and autophagy activation after RNS. Collectively, IL-33 provides potential neuroprotection through suppressing apoptosis, autophagy and at least in part by NF-κB-mediated inflammatory pathways after RNS.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
DOI：
10.1073/pnas.1406425111
发表时间：
2014-06-10
影响因子：
11.1
作者：
Lindqvist, Lisa M.;Heinlein, Melanie;Vaux, David L.
通讯作者：
Vaux, David L.
影响因子：
27.4
作者：
Manetti, Mirko;Ibba-Manneschi, Lidia;Cipriani, Paola
通讯作者：
Cipriani, Paola
影响因子：
64.5
作者：
Jin, Zhaoyu;Li, Yun;Ashkenazi, Avi
通讯作者：
Ashkenazi, Avi
SIRT1 通过促进退变的人椎间盘髓核细胞的自噬来防止细胞凋亡。
影响因子：
4.6
作者：
Jiang W;Zhang X;Hao J;Shen J;Fang J;Dong W;Wang D;Zhang X;Shui W;Luo Y;Lin L;Qiu Q;Liu B;Hu Z
通讯作者：
Hu Z