Activation of the receptor for advanced glycation end products (RAGE) exacerbates experimental autoimmune myasthenia gravis symptoms
Activation of the receptor for advanced glycation end products (RAGE) exacerbates experimental autoimmune myasthenia gravis symptoms
复制标题
晚期糖基化终产物（RAGE）受体的激活会加剧实验性自身免疫性重症肌无力症状
DOI：
10.1016/j.clim.2011.04.013
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发表时间：
2011-10-01
影响因子：
8.6
通讯作者：
Li, Hulun
中科院分区：
文献类型：
--
作者：
Mu, Lili;Zhang, Yao;Li, Hulun
RAGE属于免疫球蛋白超家族，作为包括S100B在内的多种免疫调节分子的配体，已被证明对T细胞介导的自身免疫性疾病很重要。在这种情况下，我们假设RAGE也可能影响B细胞介导的T细胞依赖性自身免疫性疾病。采用重症肌无力（MG）动物模型EAMG进行验证。我们发现RAGE和S100B的表达在EAMG过程中增加，RAGE和S100B的相互作用影响了Th1/Th2/Th17/Treg细胞平衡，上调了achr特异性T细胞的增殖。此外，体外添加S100B刺激与COX-2上调相关的脾细胞活性。NS-398是一种选择性COX-2抑制剂，可有效降低S100B介导的achr特异性抗体分泌脾细胞的活性。这些发现表明RAGE和S100B之间的相互关系促进了EAMG的发展，强调了了解EAMG疾病机制作为开发治疗MG的新疗法的重要性。(C) 2011爱思唯尔公司版权所有。
RAGE belongs to immunoglobulin superfamily and serves as a ligand for various immunoregulatory molecules including S100B that has been demonstrated important to T cell mediated autoimmune diseases. In this context, we hypothesized that RAGE could also impact B cell mediated, T cell-dependent autoimmune diseases. This was tested using myasthenia gravis (MG) animal model, EAMG. We show that expression of both RAGE and S100B are increased during EAMG and the interaction between RAGE and S100B affected the Th1/Th2/Th17/Treg cell equilibrium, up-regulate AChR-specific T cell proliferation. Furthermore, addition of S100B in vitro stimulated splenocyte activity linked to COX-2 up-regulation. NS-398, a selective COX-2 inhibitor, effectively diminished S100B mediated activity of AChR-specific antibody secreting splenocytes. These findings suggested that a reciprocal relationship between RAGE and S100B promoted the development of EAMG, highlighting the importance of understanding the mechanisms of EAMG disease as a means of developing new therapies for the treatment of MG. (C) 2011 Elsevier Inc. All rights reserved.