Potent anti-inflammatory activity of the lectin-like domain of TNF in joints.
Potent anti-inflammatory activity of the lectin-like domain of TNF in joints.
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DOI：
10.3389/fimmu.2022.1049368
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发表时间：
2022
影响因子：
7.3
通讯作者：
Rocha, Francisco Airton Castro
中科院分区：
文献类型：
--
作者：
Pinto, Ana Carolina Matias Dinelly;Nunes, Rodolfo de Melo;Nogueira, Igor Albuquerque;Fischer, Bernhard;Lucas, Rudolf;Girao-Carmona, Virginia Claudia Carneiro;de Oliveira, Vivian Louise Soares;Amaral, Flavio Almeida;Schett, Georg;Rocha, Francisco Airton Castro
鉴于肿瘤坏死因子（tumor necrosis factor， TNF）在关节破坏中的重要作用，TNF抑制剂，包括中和性抗TNF抗体和可溶性TNF受体构建物，是治疗类风湿性关节炎（RA）等关节病的常用疗法。然而，并非所有患者都能获得缓解；此外，还存在对这些病原体感染易感性增加的风险。在空间上与其受体结合位点不同，TNF含有凝集素样结构域，其发挥独特的功能，可被17残基茄碱肽模仿。该结构域结合特定的寡糖，如N ' N ' -二乙酰壳聚糖，并直接靶向上皮钠通道的α亚基。索拉肽在急性肺损伤和肾小球肾炎模型中显示出抗炎作用。在这项研究中，我们评估了TNF的凝集素样结构域是否可以减轻小鼠免疫介导性关节炎的发展。在抗原诱导的关节炎模型中，与对照组相比，solnatide减少了细胞内流和促炎介质进入关节的释放，与水肿和组织损伤的减少有关，这表明TNF通过其凝集素样结构域在急性关节炎症模型中具有抗炎作用。
In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N′N′-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.
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DOI：
10.1038/nrrheum.2015.169
发表时间：
2016-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Kalliolias GD;Ivashkiv LB
通讯作者：
Ivashkiv LB
影响因子：
4.9
作者：
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影响因子：
7.3
作者：
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通讯作者：
Stammberger U
影响因子：
6.4
作者：
Daulouède, S;Bouteille, B;Vincendeau, P
通讯作者：
Vincendeau, P
DOI：
10.1164/rccm.201405-0833oc
发表时间：
2014-09-01
影响因子：
24.7
作者：
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通讯作者：
Lucas, Rudolf