Mode of Action of Aspirin in Experimental Autoimmune Encephalomyelitis.
Mode of Action of Aspirin in Experimental Autoimmune Encephalomyelitis.
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DOI：
10.1089/dna.2019.4814
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发表时间：
2019-07
影响因子：
3.1
通讯作者：
Swarupa Pahan;K. Pahan
中科院分区：
文献类型：
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作者：
Swarupa Pahan;K. Pahan
多发性硬化症（MS）是中枢神经系统的慢性和使人衰弱的自身免疫性疾病，其中自身免疫性T细胞破坏髓鞘，从而引起病变、损伤和神经元功能障碍。实验性自身免疫性脑脊髓炎（EAE）是MS的动物模型，其对于测试针对MS的新治疗方法特别有用。阿司匹林（乙酰水杨酸）是世界上最古老且广泛使用的药物之一，并且最近已经显示低剂量阿司匹林能够抑制小鼠中EAE的疾病过程。这种自身免疫性疾病过程的根本原因之一是表达Foxp 3的抗自身免疫调节性T细胞（T细胞）的减少和/或抑制以及自身免疫辅助性T细胞1（Th 1）和Th 17细胞的相关增加。阿司匹林可上调Th 1和Th 17应答，降低Th 1和Th 17应答。因此，抑制TAE消除了阿司匹林对EAE的保护作用，表明阿司匹林通过TAE保护EAE。虽然有几种机制可以在免疫损伤下维持TGFAP，但阿司匹林可以增加白细胞介素-11（IL-11）（一种免疫调节细胞因子）的水平，而IL-11单独就足以保护TGFAP。阿司匹林是一种多功能分子，通过激活cAMP反应元件结合（CREB），促进CREB向IL-11基因启动子的募集，刺激脾细胞IL-11的转录。因此，低剂量阿司匹林似乎通过CREB介导的IL-11-Treg通路的刺激来保护EAE，并且阿司匹林可能在MS中具有治疗重要性。
Multiple sclerosis (MS) is a chronic and debilitating autoimmune disorder of the central nervous system in which the autoimmune T cells destroy myelin, thus causing lesion, damage, and neuronal dysfunction. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is particularly useful for testing new therapeutic approaches against MS. Aspirin (acetyl salicylic acid) is one of the oldest and widely used medicines in the world, and recently it has been shown that low-dose aspirin is capable of suppressing the disease process of EAE in mice. One of the root causes of this autoimmune disease process is the decrease and/or suppression of Foxp3-expressing anti-autoimmune regulatory T cells (Tregs) and associated increase in autoimmune T-helper 1 (Th1) and Th17 cells. Aspirin upregulates Tregs and decreases Th1 and Th17 responses. Accordingly, the suppression of Tregs abrogates the protective effect of aspirin on EAE, indicating that aspirin protects EAE via Tregs. While there are several mechanisms for the maintenance of Tregs under immune insults, aspirin increases the level of interleukin-11 (IL-11), an immunomodulatory cytokine, and IL-11 alone is sufficient to protect Tregs. Being a multifunctional molecule, aspirin stimulates the activation of cAMP-response element-binding (CREB) to promote the recruitment of CREB to the IL-11 gene promoter and stimulate the transcription of IL-11 in splenocytes. Therefore, it appears that low-dose aspirin protects EAE via CREB-mediated stimulation of IL-11-Treg pathway and that aspirin may have therapeutic importance in MS.