Institute of Drug Research, School of Pharmacy, Faculty of Medicine, Institute of Life Sciences, The Hebrew University, POB 12065, 91120 Jerusalem, Israel.
J Autoimmun. 2010 Aug;35(1):98-106. doi: 10.1016/j.jaut.2010.03.004.
The purpose of the present study was to develop a peptide for treatment of multiple sclerosis (MS). We have tested the effect of a novel anti-inflammatory peptide (KGHYAERVG, termed IIIM1) on experimental autoimmune encephalitis (EAE), an animal model of MS. Our findings demonstrate significant reduction in neurological score following oral administration of IIIM1. Structural studies revealed that the entire peptide is required for activity. The peptide caused significant reduction in IL17, interferon gamma, IL23 and IL12 production by isolated splenocytes and concomitant elevation of anti-inflammatory cytokines. IIIM1 elevated T regulatory cells (Tregs, CD4(+)CD25(+)FoxP3(+)) in brain and spleen of EAE mice. Similar proliferative effect was observed in isolated human and mouse Tregs in vitro. Stimulation of Tregs by IIIM1 caused production of a new peptide termed RA1 present in Oryza Sativa Japonica group. This Japanese rice peptide ameliorated neurological symptoms in the EAE model. Similar beneficial effect was observed upon oral administration of an extract of Japanese rice. In conclusion, oral treatment with IIIM1 ameliorates EAE symptoms via stimulation of Tregs to proliferate and produce RA1 which reduces EAE symptoms. RA1 might be involved in the relatively low prevalence of MS in Japan and other Japanese rice-eating populations.
本研究旨在开发一种用于多发性硬化症（MS）治疗的肽。我们测试了一种新型抗炎肽（KGHYAERVG，称为 IIIM1）对实验性自身免疫性脑脊髓炎（EAE）的影响，EAE 是 MS 的动物模型。我们的研究结果表明，口服 IIIM1 后神经评分显著降低。结构研究表明，整个肽都具有活性。该肽可显著减少分离脾细胞产生的 IL17、干扰素γ、IL23 和 IL12，并同时升高抗炎细胞因子。III M1 在 EAE 小鼠的脑和脾中升高 T 调节细胞（Tregs，CD4(+)CD25(+)FoxP3(+)）。在体外分离的人和小鼠 Tregs 中也观察到类似的增殖效应。III M1 刺激 Tregs 产生一种在 Oryza Sativa Japonica 组中存在的新肽，称为 RA1。这种日本米肽可改善 EAE 模型中的神经症状。口服日本米提取物也观察到类似的有益效果。总之，口服 IIIM1 通过刺激 Tregs 增殖并产生 RA1 来改善 EAE 症状，从而减轻 EAE 症状。RA1 可能与日本和其他食用日本米人群中 MS 的低患病率有关。
