INTERLEUKIN-33 IS RELEASED IN SPINAL CORD AND SUPPRESSES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN MICE
INTERLEUKIN-33 IS RELEASED IN SPINAL CORD AND SUPPRESSES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN MICE
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Interleukin-33 在脊髓中释放并抑制小鼠实验性自身免疫性脑脊髓炎
DOI：
10.1016/j.neuroscience.2015.09.019
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发表时间：
2015-11-12
期刊：
影响因子：
3.3
通讯作者：
Zheng, F.
中科院分区：
文献类型：
--
作者：
Chen, H.;Sun, Y.;Zheng, F.
白细胞介素-33 （IL-33）通常作为非组蛋白染色质相关蛋白在细胞核中表达。经坏死细胞被动释放后，作为IL-1家族成员发挥作用。IL-33在中枢神经系统（CNS）中高表达，IL-33是否在中枢神经系统中主动释放并参与实验性自身免疫性脑脊髓炎（EAE）尚不清楚。在本研究中，我们发现IL-33和受体ST2在幼稚小鼠脊髓中表达。与未发病时相比，EAE发病前、发病期和高峰期脊髓细胞内IL-33显著降低，细胞外IL-33显著升高。在慢性阶段，情况正好相反。细胞内IL-33的减少与脑电过程中星形胶质细胞的激活和原位神经元的损伤有关。星形胶质细胞在体外炎症刺激下积极分泌IL-33。此外，中枢神经系统来源的IL-33的阻断加剧了EAE的发展。我们的数据表明，激活的星形胶质细胞和受损的神经元在EAE过程中积极释放IL-33。它通过自分泌或旁分泌方式在EAE的发展中起抑制作用。我们的发现有助于了解中枢神经系统来源的IL-33的释放特征和功能，并为多发性硬化症提供潜在的治疗靶点。(c) 2015年。Elsevier Ltd.出版。版权所有。
Interleukin-33 (IL-33) is usually expressed in the nucleus as a non-histone chromatin-associated protein. After passively released by necrotic cells, it functions as an IL-1 family member. IL-33 is highly expressed in the central nervous system (CNS), whether IL-33 is actively released in the CNS and involved in experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we found that IL-33 and receptor ST2 were expressed in the spinal cord of naive mice. Compared to naive situation, the intracellular IL-33 was dramatically decreased and extracellular IL-33 was markedly increased in the spinal cord in the pre-onset, onset and peak stage of EAE. In the chronic stage, the reverse happened. The decrease of intracellular IL-33 was related to the activation of astrocytes and the damage of neurons in situ during EAE. Astrocytes secreted IL-33 actively upon inflammatory stimulation in vitro. Furthermore, blockage of the CNS-derived IL-33 exacerbated EAE development. Our data demonstrated that IL-33 was released by activated astrocytes actively, and by damaged neurons during EAE. It plays a suppressive role in EAE development via an autocrine or paracrine manner. Our findings are helpful to understand the release feature and function of the CNS-derived IL-33 and supply a potential therapeutic target for multiple sclerosis. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.