ACTIVATION OF THE ADENOSINE A2A RECEPTOR ATTENUATES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AND IS ASSOCIATED WITH INCREASED INTRACELLULAR CALCIUM LEVELS
ACTIVATION OF THE ADENOSINE A2A RECEPTOR ATTENUATES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AND IS ASSOCIATED WITH INCREASED INTRACELLULAR CALCIUM LEVELS
复制标题
腺苷 A2A 受体的激活可减轻实验性自身免疫性脑脊髓炎，并与细胞内钙水平增加相关
DOI：
10.1016/j.neuroscience.2016.05.028
复制
发表时间：
2016-08-25
期刊：
影响因子：
3.3
通讯作者：
Li, Hulun
中科院分区：
文献类型：
--
作者：
Liu, Yumei;Zou, Haifeng;Li, Hulun
多发性硬化症（MS）是一种常见的自身免疫性疾病，不可避免地会导致炎性神经脱髓鞘。然而，仍然缺乏和迫切需要一种有效的方法来防止其发展。最近，腺苷A2 A受体（A2 AR）已成为一种新的炎症调节剂。操纵A2 AR活性可以抑制MS过程并防止神经损伤。为了验证这一假设，我们用选择性A2 AR激动剂CGS 21680（CGS）治疗了小鼠实验性自身免疫性脑脊髓炎（EAE），一种MS模型。我们评估了CGS对EAE进展的病理特征的影响，包括CNS细胞浸润、炎性细胞因子表达、淋巴细胞增殖和细胞表面标志物。CGS治疗显著抑制特异性淋巴细胞增殖，减少CD 4 + T淋巴细胞浸润，并减弱炎性细胞因子的表达，从而抑制EAE的进展。我们首次证实CGS可增加小鼠淋巴细胞内钙离子浓度（[Ca ~（2+）]i），这可能是CGS诱导的A_2AR激活对EAE进展的抑制作用的潜在机制。我们的研究结果强烈表明，A2 AR是MS的潜在治疗靶点，并提供了对A2 AR激动剂作用机制的深入了解，这可能为这种疾病提供治疗选择。(C)2016由Elsevier Ltd代表IBRO发布。
Multiple sclerosis (MS) is a common autoimmune disease that inevitably causes inflammatory nerve demyelination. However, an effective approach to prevent its course is still lacking and urgently needed. Recently, the adenosine A2A receptor (A2AR) has emerged as a novel inflammation regulator. Manipulation of A2AR activity may suppress the MS process and protect against nerve damage. To test this hypothesis, we treated murine experimental autoimmune encephalomyelitis (EAE), a model for MS, with the selective A2AR agonist, CGS21680 (CGS). We evaluated the effects of CGS on the pathological features of EAE progression, including CNS cellular infiltration, inflammatory cytokine expression, lymphocyte proliferation, and cell surface markers. Treatment with CGS significantly suppressed specific lymphocyte proliferation, reduced infiltration of CD4+ T lymphocytes, and attenuated the expression of inflammatory cytokines, which in turn inhibited the EAE progression. For the first time, we demonstrate that CGS can increase the intracellular calcium concentration ([Ca2+]i) in murine lymphocytes, which may be the mechanism underlying the suppressive effects of CGS- induced A2AR activation on EAE progression. Our findings strongly suggest that A2AR is a potential therapeutic target for MS and provide insight into the mechanism of action of A2AR agonists, which may offer a therapeutic option for this disease. (C) 2016 Published by Elsevier Ltd on behalf of IBRO.