Protection Against Arthritis by the Parasitic Worm Product ES-62, and Its Drug-Like Small Molecule Analogues, Is Associated With Inhibition of Osteoclastogenesis

Frontiers in Immunology
J DoonanW Harnett

Abstract

The immunomodulatory actions of parasitic helminth excretory-secretory (ES) products that serendipitously protect against development of chronic inflammatory disorders are well established: however, knowledge of the interaction between ES products and the host musculoskeletal system in such diseases is limited. In this study, we have focused on ES-62, a glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties, and also two synthetic drug-like PC-based small molecule analogues (SMAs) that mimic ES-62's immunomodulatory activity. We have previously shown that each of these molecules prevents development of pathology in collagen-induced arthritis (CIA), a model of the musculoskeletal disease rheumatoid arthritis (RA) and reflecting this, we now report that ES-62 and its SMAs, modify bone remodeling by altering bone marrow progenitors and thus impacting on osteoclastogenesis. Consistent with this, we find that these molecules inhibit functional osteoclast differentiation in vitro. Furthermore, this appears to be achieved by induction of anti-oxidant response gene expression, thereby resulting in reduction of the reactive ...Continue Reading

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Citations

Jun 28, 2019·Current Topics in Medicinal Chemistry·Puvvada Kalpana Murthy
Oct 30, 2018·Frontiers in Immunology·Amin ZakeriPeter Nejsum
Nov 22, 2019·Frontiers in Veterinary Science·Irina V SaltykovaPaul J Brindley
Oct 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·James DoonanWilliam Harnett
Apr 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Phurpa WangchukAlex Loukas
Oct 6, 2020·Frontiers in Immunology·Sina BohnackerJulia Esser-von Bieren

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Methods Mentioned

BETA
SMAs
FACS
FCS
Assay
PCR
flow cytometry
SMA

Software Mentioned

FlowJo
Image J
ImageJ

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Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.