Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice. (12th November 2015)

• Record Type: Journal Article
• Authors: Chen, H.; Sun, Y.; Lai, L.; Wu, H.; Xiao, Y.; Ming, B.; Gao, M.; Zou, H.; Xiong, P.; Xu, Y.; Tan, Z.; Gong, F.; Zheng, F.
• Is Part Of: Neuroscience. Volume 308(2015)
• Page Start: 157
• Page End: 168
• Publication Date: 2015-11-12
• Subjects: ANOVA analysis of variance -- CNS central nervous system -- CSF cerebrospinal fluids -- DCs dendritic cells -- EAE experimental autoimmune encephalomyelitis -- GFAP Glial fibrillary acidic protein -- HMGB1 high mobility group box 1 -- ICV intracerebroventricular -- IL-33 interleukin-33 -- LFB Luxol Fast Blue -- MS multiple sclerosis -- NAWM normal appearing white matter -- NeuN Neuronal nuclei -- PBS phosphate-buffered saline -- SD standard deviation -- SEM standard error of the mean -- SPF specific pathogen-free -- Th helper T cell -- TNF-α tumor necrosis factor-alpha -- Treg regulatory T cell; interleukin-33 -- experimental autoimmune encephalomyelitis -- central nervous system -- astrocyte -- neuron; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.09.019
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: IL-33 is released in the spinal cord during EAE. Astrocytes secrete IL-33 actively upon inflammatory stimulation. Blockage of the CNS local IL-33 exacerbates EAE development. IL-33 is expressed both in the nuclei and cytoplasm of neurons in physiological situation. Abstract: 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 naïve 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.