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

Autor: James Doonan, David Thomas, Michelle H. Wong, Hazel J. Ramage, Lamyaa Al-Riyami, Felicity E. Lumb, Kara S. Bell, Karen J. Fairlie-Clarke, Colin J. Suckling, Kathrin S. Michelsen, Hui-Rong Jiang, Anne Cooke, Margaret M. Harnett, William Harnett
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Molecules, Vol 23, Iss 10, p 2669 (2018)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules23102669
Popis: 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.
Databáze: Directory of Open Access Journals
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