Protection Against Arthritis by the Parasitic Worm Product ES-62, and Its Drug-Like Small Molecule Analogues, Is Associated With Inhibition of Osteoclastogenesis.
Protection Against Arthritis by the Parasitic Worm Product ES-62, and Its Drug-Like Small Molecule Analogues, Is Associated With Inhibition of Osteoclastogenesis.
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DOI：
10.3389/fimmu.2018.01016
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发表时间：
2018
影响因子：
7.3
通讯作者：
Harnett W
中科院分区：
文献类型：
--
作者：
Doonan J;Lumb FE;Pineda MA;Tarafdar A;Crowe J;Khan AM;Suckling CJ;Harnett MM;Harnett W
寄生性蠕虫排泄分泌 (ES) 产品的免疫调节作用可以偶然预防慢性炎症性疾病的发展，这一作用已得到充分证实：然而，对于此类疾病中 ES 产品与宿主肌肉骨骼系统之间相互作用的了解有限。在这项研究中，我们重点关注 ES-62，这是一种由啮齿动物丝虫线虫 Acanthocheilonema viteae 分泌的糖蛋白，它通过共价连接的磷酸胆碱 (PC) 部分发挥免疫调节作用，同时还有两种模拟 ES-62 免疫调节活性的合成药物样 PC 基小分子类似物 (SMA)。我们之前已经表明，这些分子中的每一种都可以防止胶原诱导的关节炎（CIA）（一种肌肉骨骼疾病类风湿性关节炎（RA）的模型）的病理发展，并反映了这一点，我们现在报告ES-62及其SMA通过改变骨髓祖细胞来改变骨重塑，从而影响破骨细胞生成。与此一致的是，我们发现这些分子在体外抑制功能性破骨细胞分化。此外，这似乎是通过诱导抗氧化反应基因表达来实现的，从而导致活性氧产生的减少，而活性氧是RA等肌肉骨骼疾病中破骨细胞生成增加所必需的。
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 oxygen species production that is necessary for the increased osteoclastogenesis witnessed in musculoskeletal diseases like RA.
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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
DOI：
10.1074/jbc.m113.478545
发表时间：
2013-08-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kanzaki H;Shinohara F;Kajiya M;Kodama T
通讯作者：
Kodama T
影响因子：
3.7
作者：
Akchurin T;Aissiou T;Kemeny N;Prosk E;Nigam N;Komarova SV
通讯作者：
Komarova SV
DOI：
10.1016/j.jaci.2016.07.007
发表时间：
2016-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Maizels RM;McSorley HJ
通讯作者：
McSorley HJ
影响因子：
6.4
作者：
Goodridge, HS;Marshall, FA;Harnett, W
通讯作者：
Harnett, W