白细胞介素-18 与 NKCC1 相互作用,介导脑出血后的脑损伤

IF 3.7 Q2 IMMUNOLOGY
Beibei Xu , Hao Li , He Zheng , Zhongyu Gao , Zhigang Miao , Xingshun Xu , Hao Yang , Yi Yang
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引用次数: 0

摘要

白细胞介素 18(IL-18)是一种促炎细胞因子,与包括脑血管疾病和精神疾病在内的多种神经系统疾病有关。之前的一项研究观察到,IL-18 能激活小胶质细胞并增强颅内出血(ICH)后的炎症反应。然而,其潜在机制仍不清楚。本研究发现,在 ICH 后的早期阶段,IL-18 和 IL-18 受体(IL-18 R)主要由神经元分泌,而在 ICH 后 12-24 h,小胶质细胞成为主要来源。同时,IL-18 R 在 ICH 后的表达水平升高,IL-18 R 与 IL-18 的结合亲和力增强。随后,IL-18 R的缺乏减轻了ICH后小鼠的神经功能损伤和随后的炎症通路激活。此外,我们的研究结果表明,IL-18 诱导的 ICH 后神经损伤可能是由 IL18R 和 NKCC1 之间的相互作用介导的。值得注意的是,NKCC1 抑制剂能挽救 ICH 后的神经损伤。总之,我们的研究表明,靶向 IL-18/IL-18R/NKCC1 通路可能是减轻 ICH 后继发性脑损伤的有效治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage
Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhage (ICH). However, the underlying mechanism remains unclear. In the present study, we found that IL-18 and IL-18 receptor (IL-18 R) are primarily secreted by neurons during the early stages after ICH, with microglia becoming the predominant source at 12–24 h after ICH. Meanwhile, the expression level of IL-18 R increased following ICH, along with an augmentation in the binding affinity of IL-18 R to IL-18. Subsequently, the deficiency of IL-18 R mitigated neurological impairment and subsequent activation of inflammatory pathways in mice post-ICH. Moreover, our findings suggest that IL-18-induced neurological injury after ICH may be mediated by the interaction between IL18R and NKCC1. Significantly, the NKCC1 inhibitor rescued the neurologic injury after ICH. In conclusion, our study suggests that targeting the IL-18/IL-18R/NKCC1 pathway could be an effective therapeutic strategy to attenuate secondary brain injury after ICH.
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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
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审稿时长
97 days
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