The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis
The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis
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DOI：
10.1136/ard.2007.073502
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发表时间：
2008-04-01
影响因子：
27.4
通讯作者：
Harnett, W.
中科院分区：
文献类型：
--
作者：
Harnett, M. M.;Kean, D. E.;Harnett, W.
目的：在寄生虫感染流行的国家，自身免疫性疾病相对罕见，这导致寄生虫衍生的免疫调节剂可以防止其发展的假设。与此相一致，我们以前已经证明，ES-62，62 kDa的磷酸胆碱（PC）的糖蛋白分泌的丝虫，可以发挥抗炎作用，在鼠胶原诱导的关节炎（CIA）模型和人类类风湿性关节炎衍生的滑膜组织培养。作为开发基于ES-62的药物的第一步，本研究的目的是确定ES-62的PC部分是否负责其抗炎作用。我们比较了无PC形式的重组ES-62（rES-62）和合成的PC-卵清蛋白缀合物（OVA-PC）与天然ES-62（rES-62）的抗炎活性。62在CIA模型和类风湿关节炎患者的滑膜组织中。ES-62在CIA中的抗炎作用似乎依赖于PC部分，如在测试OVA-PC时观察到的疾病严重程度的降低以及胶原特异性T辅助细胞因子1产生的抑制所示，而不是rES-62。有趣的是，PC的抗炎活性与抗胶原蛋白IgG 2a水平的降低无关。此外，ES-62介导的抑制干扰素-C从人类患者组织可以模仿OVA-PC，但不是rES-62或ovalbumin.Conclusions：在丝虫病流行的国家，减少炎症性疾病，如类风湿性关节炎的检测可能是因为ES-62的PC部分的抗炎作用。因此，PC可能为开发新型、安全的免疫调节疗法提供起点。
Objective: In countries where parasitic infections are endemic, autoimmune disease is relatively rare, leading to the hypothesis that parasite-derived immunomodulators may protect against its development. Consistent with this, we have previously demonstrated that ES-62, a 62 kDa phosphorylcholine (PC)-containing glycoprotein that is secreted by filarial nematodes, can exert anti-inflammatory action in the murine collagen-induced arthritis (CIA) model and human rheumatoid arthritisderived synovial tissue cultures. As a first step to developing ES-62-based drugs, the aim of this study was to determine whether the PC-moiety of ES-62 was responsible for its anti-inflammatory actions.Methods: We compared the anti-inflammatory activity of a PC-free form of recombinant ES-62 (rES-62) and a synthetic PC-ovalbumin conjugate (OVA-PC) with that of native ES-62 in the CIA model and synovial tissues from patients with rheumatoid arthritis.Results: The anti-inflammatory actions of ES-62 in CIA appear to be dependent on the PC moiety as indicated by the reduction in severity of disease and also suppression of collagen-specific T helper 1 cytokine production observed when testing OVA-PC, but not rES-62. Interestingly, the anti-inflammatory activity of PC did not correlate with a reduction in anti-collagen IgG2a levels. Also, the ES-62-mediated suppression of interferon-c from human patient tissues could be mimicked by OVA-PC but not rES-62 or ovalbumin.Conclusions: In countries where filariasis is endemic the reduced detection of inflammatory diseases, such as rheumatoid arthritis may be because of the anti-inflammatory action of the PC moieties of ES-62. PC may thus provide the starting point for the development of novel, safe immunomodulatory therapies.