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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
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-in...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222842/ https://www.ncbi.nlm.nih.gov/pubmed/30336585 http://dx.doi.org/10.3390/molecules23102669 |
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author | Doonan, James Thomas, David Wong, Michelle H. Ramage, Hazel J. Al-Riyami, Lamyaa Lumb, Felicity E. Bell, Kara S. Fairlie-Clarke, Karen J. Suckling, Colin J. Michelsen, Kathrin S. Jiang, Hui-Rong Cooke, Anne Harnett, Margaret M. Harnett, William |
author_facet | Doonan, James Thomas, David Wong, Michelle H. Ramage, Hazel J. Al-Riyami, Lamyaa Lumb, Felicity E. Bell, Kara S. Fairlie-Clarke, Karen J. Suckling, Colin J. Michelsen, Kathrin S. Jiang, Hui-Rong Cooke, Anne Harnett, Margaret M. Harnett, William |
author_sort | Doonan, James |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6222842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62228422018-11-13 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 Doonan, James Thomas, David Wong, Michelle H. Ramage, Hazel J. Al-Riyami, Lamyaa Lumb, Felicity E. Bell, Kara S. Fairlie-Clarke, Karen J. Suckling, Colin J. Michelsen, Kathrin S. Jiang, Hui-Rong Cooke, Anne Harnett, Margaret M. Harnett, William Molecules Article 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. MDPI 2018-10-17 /pmc/articles/PMC6222842/ /pubmed/30336585 http://dx.doi.org/10.3390/molecules23102669 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Doonan, James Thomas, David Wong, Michelle H. Ramage, Hazel J. Al-Riyami, Lamyaa Lumb, Felicity E. Bell, Kara S. Fairlie-Clarke, Karen J. Suckling, Colin J. Michelsen, Kathrin S. Jiang, Hui-Rong Cooke, Anne Harnett, Margaret M. Harnett, William 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222842/ https://www.ncbi.nlm.nih.gov/pubmed/30336585 http://dx.doi.org/10.3390/molecules23102669 |
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