Treatment with 6-Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis
Treatment with 6-Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis
复制标题
6-姜酚治疗可调节树突状细胞活性并减轻实验性自身免疫性脑脊髓炎的严重程度
DOI：
10.1002/mnfr.201801356
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发表时间：
2019-07-22
影响因子：
5.2
通讯作者：
Zhang, Yuan
中科院分区：
文献类型：
--
作者：
Han, Juan-Juan;Li, Xing;Zhang, Yuan
范围多发性硬化症(MS)是一种炎症性脱髓鞘自身免疫性疾病，在全球范围内发病率不断上升，但病因不明。6-姜酚(6-GIN)是生姜中发现的一种主要的饮食化合物，具有免疫调节活性。然而，它在自身免疫性疾病中的作用以及潜在的机制尚不清楚。本研究采用MS动物模型，观察6-GIN能否有效改善实验性自身免疫性脑脊髓炎(EAE)小鼠的临床病情。用流式细胞仪、酶联免疫吸附试验和组织病理学方法检测EAE小鼠的外周炎症和神经炎症，结果表明6-GIN能显著抑制炎症细胞从外周向中枢神经系统的侵袭，减少神经炎症和脱髓鞘。流式细胞仪分析、ELISA法和定量聚合酶链式反应显示，6-GIN可抑制脂多糖诱导的树突状细胞(DC)活化，诱导耐受树突状细胞(DC)。免疫印迹分析显示，核因子-kappaB和丝裂原活化蛋白激酶这两个关键的炎症信号调节因子的磷酸化在6-GIN处理的DC中受到显著抑制。结论6-GIN可通过对DC的直接调节作用，作为一种新型抗炎药用于治疗MS等自身免疫性疾病。
Scope Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder, with increasing incidence worldwide but unknown etiology. 6-Gingerol (6-GIN), a major dietary compound found in ginger rhizome, has immunomodulatory activity. However, its role in autoimmune diseases, as well as the underlying mechanisms, are unclear. In this study, it is evaluated if 6-GIN can effectively ameliorate the clinical disease severity of experimental autoimmune encephalomyelitis, an animal model of MS. Methods and results Clinical scores of experimental autoimmune encephalomyelitis (EAE) mice are recorded daily. Inflammation of periphery and neuroinflammation of EAE mice are determined by flow cytometry analysis, ELISA, and histopathological analysis, and results show that 6-GIN significantly inhibits inflammatory cell infiltration from the periphery into the central nervous system and reduces neuroinflammation and demyelination. Flow cytometry analysis, ELISA, and quantitative PCR show that 6-GIN could suppress lipolysaccharide-induced dendritic cell (DC) activation and induce the tolerogenic DCs. Immunoblot analysis reveals that the phosphorylation of nuclear factor-kappa B and mitogen-activated protein kinase, two critical regulators of inflammatory signaling, are significantly inhibited in 6-GIN-treated DCs. Conclusion The results of this study demonstrate that 6-GIN has significant potential as a novel anti-inflammatory agent for the treatment of autoimmune diseases such as MS via direct modulatory effects on DCs.