Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models
Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models
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DOI：
10.1002/mnfr.201500222
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发表时间：
2015-09-01
影响因子：
5.2
通讯作者：
van de Loo, Fons A. J.
中科院分区：
文献类型：
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作者：
Arntz, Onno J.;Pieters, Bartijn C. H.;van de Loo, Fons A. J.
适用范围：本研究表明，对自发性多发性关节炎的IL-1 Ra-缺陷小鼠和胶原诱导arthritis.Methods和结果：BMEVs的牛乳衍生的细胞外囊泡（BMEVs）的效果从半脱脂牛奶中分离出超离心和动态光散射和电子显微镜的粒径约为100 nm。BMEV表达外泌体标记物CD 63、免疫调节microRNA（miR-30 a、-223、-92a）和乳特异性β-酪蛋白和β-乳球蛋白mRNA。在体外，PKH-67标记的BMEV被RAW264.7、脾细胞和肠细胞摄取，如通过流式细胞术和共聚焦显微镜所确定的。IL-1 Ra（-/-）小鼠在出生后第5周至第15周通过每日口服管饲法接受BMEV，胶原诱导的关节炎小鼠在免疫前1周至第40天通过饮用水接受BMEV。肉眼观察，BMEV治疗延迟了关节炎的发作，组织学显示两种模型中的软骨病理学和骨髓炎症减少。BMEV处理还降低了MCP-1和IL-6的血清水平及其由脾细胞产生的水平。BMEV治疗减少了抗胶原蛋白IgG 2a的水平，这是伴随着减少脾Th 1（Tbet）和Th 17（ROR γ T）mRNA.Conclusion：这是第一次报告，口服BMEVs改善实验性关节炎，这值得进一步研究，以确定是否可以看到这种有益的效果在类风湿性关节炎患者。
Scope: This study shows the effect of bovine milk derived extracellular vesicles (BMEVs) on spontaneous polyarthritis in IL-1Ra-deficient mice and collagen-induced arthritis.Methods and results: BMEVs were isolated from semi-skimmed milk by ultracentrifugation and the particle size was around 100 nm by dynamic light scattering and electron microscopy. BMEVs expressed exosome marker CD63, immunoregulatory microRNA's (miR-30a, -223, -92a), and milk-specific beta-casein and beta-lactoglobulin mRNA. In vitro, PKH-67-labeled BMEVs were taken up by RAW264.7, splenocytes, and intestinal cells as determined by flow cytometry and confocal microscopy. IL-1Ra(-/-) mice received BMEVs by daily oral gavage starting at wk 5 till 15 after birth and collagen-induced arthritis mice via their drinking water starting 1 wk before immunization till day 40. Macroscopically, BMEV treatment delayed the onset of arthritis and histology showed diminished cartilage pathology and bone marrow inflammation in both models. BMEV treatment also reduced the serum levels of MCP-1 and IL-6 and their production by splenic cells. BMEV treatment diminished the anticollagen IgG2a levels, which was accompanied by reduced splenic Th1 (Tbet) and Th17 (ROR gamma T) mRNA.Conclusion: This is the first report that oral delivery of BMEVs ameliorates experimental arthritis and this warrants further research to determine whether this beneficial effect can be seen in rheumatoid arthritis patients.