Failure of the Anti-Inflammatory Parasitic Worm Product ES-62 to Provide Protection in Mouse Models of Type I Diabetes, Multiple Sclerosis, and Inflammatory Bowel Disease.
Failure of the Anti-Inflammatory Parasitic Worm Product ES-62 to Provide Protection in Mouse Models of Type I Diabetes, Multiple Sclerosis, and Inflammatory Bowel Disease.
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DOI：
10.3390/molecules23102669
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发表时间：
2018-10-17
期刊：
影响因子：
--
通讯作者：
Harnett W
中科院分区：
文献类型：
--
作者：
Doonan J;Thomas D;Wong MH;Ramage HJ;Al-Riyami L;Lumb FE;Bell KS;Fairlie-Clarke KJ;Suckling CJ;Michelsen KS;Jiang HR;Cooke A;Harnett MM;Harnett W
寄生蠕虫及其分离的分泌产物显示出作为人类过敏性和自身免疫性疾病的新型治疗方法的希望。分泌产物中最重要的是ES-62，一种来源于Acanthocheilonema viteae的糖蛋白，Acanthocheilonema viteae是沙鼠的一种丝虫线虫寄生虫，其通过共价连接的磷酸胆碱（PC）部分抗炎。已经发现ES-62在类风湿性关节炎、系统性红斑狼疮和气道高反应性的小鼠模型中保护免于疾病。此外，ES-62的新型基于PC的合成小分子类似物（SMA）最近已被证明显示出与母体分子相似的抗炎特性。尽管取得了这些成功，但我们现在表明ES-62及其SMA无法在某些自身免疫性疾病的小鼠模型中提供保护，其中其他蠕虫物种或其分泌产物可以预防疾病发展，即I型糖尿病，多发性硬化症和炎症性肠病。我们推测ES-62在这些条件下失败的原因，以及所产生的负面数据如何帮助我们进一步了解ES-62的作用机制。
Parasitic helminths and their isolated secreted products show promise as novel treatments for allergic and autoimmune conditions in humans. Foremost amongst the secreted products is ES-62, a glycoprotein derived from Acanthocheilonema viteae, a filarial nematode parasite of gerbils, which is anti-inflammatory by virtue of covalently-attached phosphorylcholine (PC) moieties. ES-62 has been found to protect against disease in mouse models of rheumatoid arthritis, systemic lupus erythematosus, and airway hyper-responsiveness. Furthermore, novel PC-based synthetic small molecule analogues (SMAs) of ES-62 have recently been demonstrated to show similar anti-inflammatory properties to the parent molecule. In spite of these successes, we now show that ES-62 and its SMAs are unable to provide protection in mouse models of certain autoimmune conditions where other helminth species or their secreted products can prevent disease development, namely type I diabetes, multiple sclerosis and inflammatory bowel disease. We speculate on the reasons underlying ES-62’s failures in these conditions and how the negative data generated may help us to further understand ES-62’s mechanism of action.
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DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
4.6
作者：
Coltherd JC;Rodgers DT;Lawrie RE;Al-Riyami L;Suckling CJ;Harnett W;Harnett MM
通讯作者：
Harnett MM
来自蠕虫筋膜的分泌蛋白抑制自动反应性T细胞反应的启动，并防止NOD小鼠中的糖尿病。
影响因子：
3.7
作者：
Lund ME;O'Brien BA;Hutchinson AT;Robinson MW;Simpson AM;Dalton JP;Donnelly S
通讯作者：
Donnelly S
影响因子：
7.3
作者：
Al-Riyami L;Pineda MA;Rzepecka J;Huggan JK;Khalaf AI;Suckling CJ;Scott FJ;Rodgers DT;Harnett MM;Harnett W
通讯作者：
Harnett W
影响因子：
2.1
作者：
Al-Riyami L;Rodgers DT;Rzepecka J;Pineda MA;Suckling CJ;Harnett MM;Harnett W
通讯作者：
Harnett W