Suppression of Experimental Autoimmune Encephalomyelitis by Ghrelin
Suppression of Experimental Autoimmune Encephalomyelitis by Ghrelin
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DOI：
10.4049/jimmunol.0803362
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发表时间：
2009-08-15
影响因子：
4.4
通讯作者：
Yamamura, Takashi
中科院分区：
文献类型：
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作者：
Theil, Michael-Mark;Miyake, Sachiko;Yamamura, Takashi
胃促生长素是最近发现的一种胃激素，具有很强的生长激素释放活性，由生长激素促分泌受体介导。虽然这种独特的内源性肽参与调节能量稳态，增加食物摄入，减少能量消耗，但其在体外抑制促炎细胞因子产生的能力表明其在体内调节炎症过程中的作用。在这里，我们研究外源性胃饥饿素对实验性自身免疫性脑脊髓炎（EAE）发展的影响，EAE是多发性硬化症的代表模型。在髓鞘少突胶质细胞糖蛋白35-55肽致敏的C57BL/6小鼠EAE模型中，我们发现从第1天至第35天隔天注射ghrelin （5 μ g/kg/天）可显著降低EAE的临床严重程度。EAE的抑制伴随着疾病高峰期胃饥饿素处理小鼠脊髓细胞浸润和小胶质细胞中促炎细胞因子如tnf - α、IL-1 β和IL-6 mRNA水平的降低，提示胃饥饿素作为抗炎激素的作用。在体外实验中，胃饥饿素一致地显著抑制lps刺激的小胶质细胞中促炎细胞因子的产生。这些结果揭示了胃饥饿素在炎症调节中的新作用，可能对人类疾病的管理产生影响。免疫学杂志，2009,33(3):2859-2866。
Ghrelin is a recently identified gastric hormone that displays strong growth hormone-releasing activity mediated by the growth hormone secretagogue receptor. While this unique endogenous peptide participates in the regulation of energy homeostasis, increases food intake, and decreases energy expenditure, its ability to inhibit the production of proinflammatory cytokines in vitro indicates its role in the regulation of inflammatory process in vivo. Here we examine the effect of exogenous ghrelin on the development of experimental autoimmune encephalomyelitis (EAE), a representative model of multiple sclerosis. In the C57BL/6 mouse model of EAE induced by sensitization to myelin oligodendrocyte glycoprotein 35-55 peptide, we found that alternate-day s.c. injections of ghrelin (5 mu g/kg/day) from day 1 to 35 significantly reduced the clinical severity of EAE. The suppression of EAE was accompanied by reduced mRNA levels of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-6 in the spinal cord cellular infiltrates and microglia from ghrelin-treated mice at the peak of disease, suggesting the role of ghrelin as an anti-inflammatory hormone. Consistently, ghrelin significantly suppressed the production of proinflammatory cytokines in LPS-stimulated microglia in vitro. These results shed light on the new role of ghrelin in the regulation of inflammation with possible implications for management of human diseases. The Journal of Immunology, 2009, 183: 2859-2866.